Publications by authors named "Thomas Laeger"

22 Publications

  • Page 1 of 1

Postprandial dynamics and response of fibroblast growth factor 21 in older adults.

Clin Nutr 2021 Jun 27;40(6):3765-3771. Epub 2021 Apr 27.

German Institute of Human Nutrition, Potsdam-Rehbrücke, Department of Nutrition and Gerontology, Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Potsdam, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Geriatrics, Berlin, Germany. Electronic address:

Background & Aims: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition.

Methods: Participants (n = 60 older; n = 60 younger) were randomized to one of four test meals: dextrose, high carbohydrate (HC), high fat (HF) or high protein (HP). Blood was drawn before and 15, 30, 60, 120, 240 min after meal ingestion. Postprandial dynamics were evaluated using repeated measures ANCOVA. FGF21 response was assessed by incremental area under the curve.

Results: Fasting FGF21 concentrations were significantly higher in older adults. FGF21 dynamics were affected by test meal (p < 0.001) and age (p = 0.013), when adjusted for BMI and fasting FGF21. Postprandial FGF21 concentrations steadily declined over 240 min in both age groups after HF and HP, but not after dextrose or HC ingestion. At 240 min, FGF21 concentrations were significantly higher in older than in younger adults following dextrose (133 pg/mL, 95%CI: 103, 172 versus 91.2 pg/mL, 95%CI: 70.4, 118; p = 0.044), HC (109 pg/mL, 95%CI: 85.1, 141 versus 70.3 pg/mL, 95%CI: 55.2, 89.6; p = 0.014) and HP ingestion (45.4 pg/mL, 95%CI: 34.4, 59.9 versus 27.9 pg/mL 95%CI: 20.9, 37.1; p = 0.018). FGF21 dynamics and response to HF were similar for both age groups.

Conclusions: The age-specific differences in postprandial FGF21 dynamics and response in healthy adults, potentially explain higher FGF21 concentrations in older age. Furthermore, there appears to be a significant impact of acute and recent protein intake on FGF21 secretion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.04.037DOI Listing
June 2021

The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells.

Mol Metab 2021 03 23;45:101151. Epub 2020 Dec 23.

German Institute of Human Nutrition (DIfE) Potsdam-Rehbruecke, Germany; German Center for Diabetes Research (DZD) Munich Neuherberg, Germany; University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Germany. Electronic address:

Objective: Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion from pancreatic β-cells.

Methods: A β-cell-specific Arfrp1 knockout mouse was phenotypically characterized. Pulldown experiments and mass spectrometry analysis were employed to screen for new ARFRP1-interacting proteins. Co-immunoprecipitation assays as well as super-resolution microscopy were applied for validation.

Results: The GTPase ARFRP1 interacts with the Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). Both proteins are co-localized at the trans-Golgi network and regulate the first and second phase of insulin secretion by controlling the plasma membrane localization of the SNARE protein SNAP25. Downregulation of both GOPC and ARFRP1 in Min6 cells interferes with the plasma membrane localization of SNAP25 and enhances its degradation, thereby impairing glucose-stimulated insulin release from β-cells. In turn, overexpression of SNAP25 as well as GOPC restores insulin secretion in islets from β-cell-specific Arfrp1 knockout mice.

Conclusion: Our results identify a hitherto unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2020.101151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811047PMC
March 2021

FGF21, not GCN2, influences bone morphology due to dietary protein restrictions.

Bone Rep 2020 Jun 31;12:100241. Epub 2019 Dec 31.

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.

Methods: Adult wild-type (WT) or KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (μCT) for changes in trabecular and cortical architecture and mass.

Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of but not . This decrease in bone did not appear after 2 weeks on the LP diet. In addition, KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture.

Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2019.100241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950640PMC
June 2020

Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH.

Nutrients 2019 Nov 8;11(11). Epub 2019 Nov 8.

Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany.

Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11112709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893460PMC
November 2019

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism.

Cell Rep 2019 06;27(10):2934-2947.e3

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Electronic address:

Reduced dietary protein intake induces adaptive physiological changes in macronutrient preference, energy expenditure, growth, and glucose homeostasis. We demonstrate that deletion of the FGF21 co-receptor βKlotho (Klb) from the brain produces mice that are unable to mount a physiological response to protein restriction, an effect that is replicated by whole-body deletion of FGF21. Mice forced to consume a low-protein diet exhibit reduced growth, increased energy expenditure, and a resistance to diet-induced obesity, but the loss of FGF21 signaling in the brain completely abrogates that response. When given access to a higher protein alternative, protein-restricted mice exhibit a shift toward protein-containing foods, and central FGF21 signaling is essential for that response. FGF21 is an endocrine signal linking the liver and brain, which regulates adaptive, homeostatic changes in metabolism and feeding behavior during protein restriction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579533PMC
June 2019

Methionine restriction prevents onset of type 2 diabetes in NZO mice.

FASEB J 2019 06 6;33(6):7092-7102. Epub 2019 Mar 6.

Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits increased circulating levels of FGF21 and merits further investigation.-Castaño-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schürmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.201900150RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529347PMC
June 2019

Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein.

J Nutr Biochem 2019 01 13;63:109-116. Epub 2018 Oct 13.

Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. Electronic address:

Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components. Primary hepatocytes were treated with different macronutrients, and Dpp4 mRNA levels and DPP4 activity were evaluated. Moreover, dietary low-protein intervention was conducted in New Zealand obese (NZO) mice, and subsequently, effects on Dpp4 expression, methylation as well as plasma concentration and activity were determined. Our results indicate that Dpp4 mRNA expression is mediated by DNA methylation in several tissues. We therefore consider the Dpp4 southern shore as tissue differentially methylated region. Amino acids increased Dpp4 expression in primary hepatocytes, whereas glucose and fatty acids were without effect. Dietary protein restriction in NZO mice increased Dpp4 DNA methylation in liver leading to diminished Dpp4 expression and consequently to lowered plasma DPP4 activity. We conclude that protein restriction in the adolescent and adult states is a sufficient strategy to reduce DPP4 which in turn contributes to improve glucose homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jnutbio.2018.09.025DOI Listing
January 2019

Dominance-diversity relationships in ant communities differ with invasion.

Glob Chang Biol 2018 10 21;24(10):4614-4625. Epub 2018 Jun 21.

Department of Experimental Diabetology (DIAB), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.

The relationship between levels of dominance and species richness is highly contentious, especially in ant communities. The dominance-impoverishment rule states that high levels of dominance only occur in species-poor communities, but there appear to be many cases of high levels of dominance in highly diverse communities. The extent to which dominant species limit local richness through competitive exclusion remains unclear, but such exclusion appears more apparent for non-native rather than native dominant species. Here we perform the first global analysis of the relationship between behavioral dominance and species richness. We used data from 1,293 local assemblages of ground-dwelling ants distributed across five continents to document the generality of the dominance-impoverishment rule, and to identify the biotic and abiotic conditions under which it does and does not apply. We found that the behavioral dominance-diversity relationship varies greatly, and depends on whether dominant species are native or non-native, whether dominance is considered as occurrence or relative abundance, and on variation in mean annual temperature. There were declines in diversity with increasing dominance in invaded communities, but diversity increased with increasing dominance in native communities. These patterns occur along the global temperature gradient. However, positive and negative relationships are strongest in the hottest sites. We also found that climate regulates the degree of behavioral dominance, but differently from how it shapes species richness. Our findings imply that, despite strong competitive interactions among ants, competitive exclusion is not a major driver of local richness in native ant communities. Although the dominance-impoverishment rule applies to invaded communities, we propose an alternative dominance-diversification rule for native communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/gcb.14331DOI Listing
October 2018

Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes.

Diabetologia 2018 06 17;61(6):1459-1469. Epub 2018 Mar 17.

Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.

Aims/hypothesis: Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism.

Methods: We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels.

Results: Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure.

Conclusion/interpretation: Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-018-4595-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449005PMC
June 2018

Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease.

Mol Metab 2017 10 4;6(10):1254-1263. Epub 2017 Aug 4.

German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany. Electronic address:

Objective: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity.

Methods: Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity. In vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to validate cell autonomous effects of DPP4 on lipid storage and insulin sensitivity.

Results: Subjects suffering from insulin resistance and NAFLD show an increased plasma DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. They furthermore show increased body weight, fat mass, adipose tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia. These effects were accompanied by increased expression of PPARγ and CD36 as well as severe insulin resistance in the liver. In agreement, treatment of HepG2 cells and primary hepatocytes with physiological concentrations of DPP4 resulted in impaired insulin sensitivity independent of lipid content.

Conclusions: Our results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2017.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641684PMC
October 2017

Low protein-induced increases in FGF21 drive UCP1-dependent metabolic but not thermoregulatory endpoints.

Sci Rep 2017 08 15;7(1):8209. Epub 2017 Aug 15.

Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.

Dietary protein restriction increases adipose tissue uncoupling protein 1 (UCP1), energy expenditure and food intake, and these effects require the metabolic hormone fibroblast growth factor 21 (FGF21). Here we test whether the induction of energy expenditure during protein restriction requires UCP1, promotes a resistance to cold stress, and is dependent on the concomitant hyperphagia. Wildtype, Ucp1-KO and Fgf21-KO mice were placed on control and low protein (LP) diets to assess changes in energy expenditure, food intake and other metabolic endpoints. Deletion of Ucp1 blocked LP-induced increases in energy expenditure and food intake, and exacerbated LP-induced weight loss. While LP diet increased energy expenditure and Ucp1 expression in an FGF21-dependent manner, neither LP diet nor the deletion of Fgf21 influenced sensitivity to acute cold stress. Finally, LP-induced energy expenditure occurred even in the absence of hyperphagia. Increased energy expenditure is a primary metabolic effect of dietary protein restriction, and requires both UCP1 and FGF21 but is independent of changes in food intake. However, the FGF21-dependent increase in UCP1 and energy expenditure by LP has no effect on the ability to acutely respond to cold stress, suggesting that LP-induced increases in FGF21 impact metabolic but not thermogenic endpoints.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-07498-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557875PMC
August 2017

FGF21 improves glucose homeostasis in an obese diabetes-prone mouse model independent of body fat changes.

Diabetologia 2017 Nov 2;60(11):2274-2284. Epub 2017 Aug 2.

Department of Experimental Diabetology (DIAB), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.

Aims/hypothesis: Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes.

Methods: Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week. Mice were treated subcutaneously with PBS or FGF21 to assess changes in glucose homeostasis, energy expenditure, food intake and other metabolic endpoints.

Results: FGF21 treatment prevented islet destruction and the onset of hyperglycaemia, and improved glucose clearance. FGF21 increased energy expenditure by inducing browning in subcutaneous white adipose tissue. However, as a result of a compensatory increased food intake, body fat did not decrease in response to FGF21 treatment, but exhibited elevated Glut4 expression.

Conclusions/interpretation: FGF21 prevents the onset of diet-induced diabetes, without changing body fat mass. Beneficial effects are mediated via white adipose tissue browning and elevated thermogenesis. Furthermore, these data indicate that obesity does not induce FGF21 resistance in NZO mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-017-4389-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448882PMC
November 2017

A global database of ant species abundances.

Ecology 2017 Mar;98(3):883-884

Department of Biology, University of Vermont, Burlington, Vermont, 05405, USA.

What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51 ,388 ant abundance and occurrence records of more than 2,693 species and 7,953 morphospecies from local assemblages collected at 4,212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type, and degree of disturbance. The aim of compiling this data set was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardized methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing data set.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ecy.1682DOI Listing
March 2017

Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2.

Cell Rep 2016 07 7;16(3):707-16. Epub 2016 Jul 7.

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Electronic address:

FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months. Gcn2 KO mice recapitulate this phenotype, but LP-induced effects on food intake, EE, and body weight subsequently begin to appear after 14 days on diet. We show that this delayed emergence of LP-induced metabolic effects in Gcn2 KO mice coincides with a delayed but progressive increase of hepatic Fgf21 expression and blood FGF21 concentrations over time. These data indicate that FGF21 is essential for the metabolic response to protein restriction but that GCN2 is only transiently required for LP-induced FGF21.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2016.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956501PMC
July 2016

Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

Metabolism 2016 06 3;65(6):805-15. Epub 2016 Mar 3.

Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808. Electronic address:

Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2016.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867053PMC
June 2016

Protein-dependent regulation of feeding and metabolism.

Trends Endocrinol Metab 2015 May 11;26(5):256-62. Epub 2015 Mar 11.

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

Free-feeding animals often face complex nutritional choices that require the balancing of competing nutrients, but the mechanisms driving macronutrient-specific food intake are poorly defined. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake and metabolism, and that dietary protein intake may be prioritized over energy intake. This review focuses on recent progress in defining the mechanisms underlying protein-specific feeding. Considering the evidence that protein powerfully regulates both food intake and metabolism, uncovering these protein-specific mechanisms may reveal new molecular targets for the treatment of obesity and diabetes while also offering a more complete understanding of how dietary factors shape both food intake and food choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tem.2015.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416985PMC
May 2015

Cerebrospinal fluid prohormone processing and neuropeptides stimulating feed intake of dairy cows during early lactation.

J Proteome Res 2015 Feb 14;14(2):823-8. Epub 2015 Jan 14.

Institute of Nutritional Physiology "Oskar Kellner", Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides. In the present study, we used a proteomic approach to analyze the neuropeptide concentrations in cerebrospinal fluid taken from dairy cows between day -18 and -10, and between day +10 and +20 relative to parturition. We found 13 proteins which were only present in samples taken before parturition, 13 proteins which were only present in samples taken after parturition, and 25 proteins which were commonly present, before and after parturition. Among them, differences in pro-neuropeptide Y, proenkephalin-A, neuroendocrine convertase-2, neurosecretory protein VGF, chromogranin-A, and secretogranin-1 and -3 concentrations relative to parturition highlight propeptides and prohormone processings involved in the control of feed intake and energy homeostasis. Scaffold analysis further emphasized an increased tone of endogenous opioids associated with the postparturient increase of feed intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr500872kDOI Listing
February 2015

FGF21 is an endocrine signal of protein restriction.

J Clin Invest 2014 Sep 18;124(9):3913-22. Epub 2014 Aug 18.

Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI74915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153701PMC
September 2014

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein.

Am J Physiol Regul Integr Comp Physiol 2014 Aug 4;307(3):R310-20. Epub 2014 Jun 4.

Pennington Biomedical Research Center, Baton Rouge, Lousiana; and

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpregu.00116.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121631PMC
August 2014

The ketone body β-hydroxybutyric acid influences agouti-related peptide expression via AMP-activated protein kinase in hypothalamic GT1-7 cells.

J Endocrinol 2012 May 22;213(2):193-203. Epub 2012 Feb 22.

Research Unit Nutritional Physiology Oskar Kellner Research Unit Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

β-Hydroxybutyric acid (BHBA) acts in the brain to influence feeding behaviour, but the underlying molecular mechanisms are unclear. GT1-7 hypothalamic cells expressing orexigenic agouti-related peptide (AGRP) were used to study the AMP-activated protein kinase (AMPK) pathway known to integrate dietary and hormonal signals for food intake regulation. In a 25 mM glucose culture medium, BHBA increased intracellular calcium concentrations and the expression of monocarboxylate transporter 1 (MCT1 (SLC16A1)). Phosphorylation of AMPK-α (PRKAA1 and PRKAA2) at Thr(172) was diminished after 2 h but increased after 4 h. Its downstream target, the mammalian target of rapamycin, was increasingly phosphorylated on Ser(2448) after 2 h but not changed after 4 h of BHBA treatment. After 4 h, BHBA treatment also increased Agrp mRNA expression. This increase was prevented by preincubation with the AMPK inhibitor Compound C. The inhibition of MCT1 activity by p-hydroxymercuribenzoate suppressed BHBA-stimulated AMPK phosphorylation but did not prevent BHBA-induced Agrp mRNA expression. This finding demonstrates that BHBA triggers the AMPK pathway resulting in orexigenic signalling under 25 mM glucose culture conditions. Under conditions of 5.5 mM glucose, however, BHBA marginally increased intracellular calcium but significantly decreased AMPK phosphorylation and Agrp mRNA expression, demonstrating that under physiological conditions BHBA reduces central orexigenic signalling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JOE-11-0457DOI Listing
May 2012

Role of beta-hydroxybutyric acid in the central regulation of energy balance.

Appetite 2010 Jun 21;54(3):450-5. Epub 2010 Apr 21.

Research Unit Nutritional Physiology "Oskar Kellner", Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

Although the phenomenon of beta-hydroxybutyric acid (BHBA) impact on satiety and thermogenesis has been described in the past decades, the underlying molecular mechanisms involved remain unresolved. Other metabolites such as glucose, fatty or branched chain amino acids are known to activate the AMP kinase pathway leading to an increase of anorexic and a decrease of orexigenic neuropeptides in the hypothalamus, one of the central regulators of energy homeostasis. Since BHBA is utilized as an energy source by the brain particularly in suckling newborns and under starving conditions, it is supposed to be a further central signal and energy providing substrate involved in the regulation of food intake. Moreover, BHBA might present a therapeutic approach for treating neuronal diseases because of its neuroprotective properties. Therefore, the purpose of this review is to summarize the known central effects of BHBA and to point out the importance of the identification of cellular pathways triggered in response to BHBA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.appet.2010.04.005DOI Listing
June 2010
-->