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Am J Physiol Endocrinol Metab 2022 May 16. Epub 2022 May 16.

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada.

Obesogens are synthetic, environmental chemicals that can disrupt endocrine control of metabolism and contribute to the risk of obesity and metabolic disease. Bisphenol A is one of the most studied obesogens. There is considerable evidence that BPA exposure is associated with weight gain, increased adiposity, poor blood glucose control and non-alcoholic fatty liver disease in animal models and human populations. Read More

Am J Physiol Endocrinol Metab 2022 May 16. Epub 2022 May 16.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

High-fat and very low-carbohydrate based ketogenic diets have gained considerable popularity as a non-pharmacological strategy for obesity, due to their potential to enhance weight loss and improve glucose homeostasis. However, the effectiveness of a ketogenic diet towards metabolic health is equivocal. In order to better understand the impact of ketogenic diets in obesity, male and female mice were fed a 60% cocoa butter-based high-fat diet for 16-weeks to induce obesity, following which mice were transitioned to either an 85% cocoa butter fat-based ketogenic diet, a 10% cocoa butter fat-based low-fat diet, or maintained on a high-fat diet for an additional 8-weeks. Read More

Am J Physiol Endocrinol Metab 2022 May 16. Epub 2022 May 16.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Brown adipose tissue (BAT) is the primary site of adaptive thermogenesis, which is involved in energy expenditure and has received much attention in the field of obesity treatment. By screening a small-molecular library of Food and Drug Administration approved drugs, pantothenic acid was identified as being able to significantly upregulate the expression of uncoupling protein 1 (UCP1), a key thermogenic protein found in BAT. Pantothenate (PA) treatment decreased adiposity, reversed fatty liver and improved glucose homeostasis via increased energy expenditure in C57BL/6J mice fed a high-fat diet. Read More

Am J Physiol Endocrinol Metab 2022 May 9. Epub 2022 May 9.

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Anatomy，School of Basic Medical Science, Southern Medical University, Guangzhou, China.

TGF-β is considered to be an important immuno regulatory cytokine. However, it remains unknown whether and how the muscle fiber specific-TGF-β signaling is directly involved in intramuscular inflammatory regulation by affecting T cells. Here, we addressed these in a mouse tibialis anterior muscle Cardiotoxin injection-induced injury repair model in MCK-Cre control or transgenic mice with TGF-β receptor II (TGF-βr2) being specifically deleted in muscle cells (SM TGF-βr2-/-). Read More

Am J Physiol Endocrinol Metab 2022 May 9. Epub 2022 May 9.

Department of Anesthesiology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi City, Xinjiang, China.

Endotoxemia is a common complication often used to model the acute inflammatory response associated with endotoxemia. Resveratrol has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties. This study explored the effect of resveratrol on endotoxemia. Read More

Am J Physiol Endocrinol Metab 2022 May 6. Epub 2022 May 6.

Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that has spread worldwide, resulting in over 6 million deaths as of March 2022. Older people have been disproportionately affected by the disease, as they have greater risk of hospitalization, are more vulnerable to severe infection, and have higher mortality than younger patients. Although effective vaccines have been rapidly developed and administered globally, several clinical trials are ongoing to repurpose existing drugs to combat severe infection. Read More

Am J Physiol Endocrinol Metab 2022 May 2. Epub 2022 May 2.

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.

Selenoprotein P (SeP; encoded by SELENOP in humans, Selenop in rodents) is a hepatokine that is upregulated in the liver of humans with type 2 diabetes. Excess SeP contributes to the onset of insulin resistance and various type 2 diabetes-related complications. We have previously reported that the long-chain saturated fatty acid, palmitic acid, upregulates Selenop expression, whereas the polyunsaturated fatty acids (PUFAs) downregulate it in hepatocytes. Read More

Am J Physiol Endocrinol Metab 2022 Apr 25. Epub 2022 Apr 25.

Mother Infant Research Institute, Tufts Medical Center, Boston, MA, United States.

Maternal obesity (body mass index, BMI>30 kg/m) is associated with greater neonatal adiposity, cord blood (CB) insulin levels, and a pro-inflammatory phenotype at birth, contributing to risk of future cardiometabolic disease in the offspring. Variation in neonatal adiposity within maternal BMI groups is underappreciated, and it remains unclear whether the metabolic impairments at birth are an outcome of maternal obesity or excess fetal fat accrual. We examined the hypothesis that CB metabolites associated with fetal fat accrual differ between offspring of normal weight and obese women. Read More

Am J Physiol Endocrinol Metab 2022 Apr 25. Epub 2022 Apr 25.

Musculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA, United States.

T-cell like factor (TCF)7l2, a key effector of canonical Wnt signaling, is highly expressed in bone but nothing is known its role in regulating osteoblast function. To test this, we generated mice with conditional disruption of Tcf7l2 gene in osteoblast lineages using Tcf7l2 floxed and Col1α2-Cre mice. Skeletal parameters were evaluated using heterozygous conditional knockdown (HCKD) mice since homozygous conditional knockout died during pregnancy or immediately after birth. Read More

Am J Physiol Endocrinol Metab 2022 06 11;322(6):E467-E479. Epub 2022 Apr 11.

Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, Washington.

Maternal exercise (ME) protects against adverse effects of maternal obesity (MO) on fetal development. As a cytokine stimulated by exercise, apelin (APN) is elevated due to ME, but its roles in mediating the effects of ME on placental development remain to be defined. Two studies were conducted. Read More

Am J Physiol Endocrinol Metab 2022 06 11;322(6):E480-E493. Epub 2022 Apr 11.

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Secreted proteins of the C1q/TNF-related protein (CTRP) family play diverse functions in different organ systems. In the brain, CTRP14/C1QL1 is required for the proper establishment and maintenance of synapses between climbing fibers and cerebellar Purkinje cells. Beyond the central nervous system, the function of CTRP14 is largely unknown. Read More

Am J Physiol Endocrinol Metab 2022 Apr 11. Epub 2022 Apr 11.

Merck & Co., Inc., South San Francisco, CA, United States.

Insulin resistance is a major public health burden that often results in other comorbidities including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. An insulin sensitizer has the potential to become a disease-modifying therapy. It remains an unmet medical need to identify therapeutics that target the insulin signaling pathway to treat insulin resistance. Read More

Am J Physiol Endocrinol Metab 2022 06 11;322(6):E494-E507. Epub 2022 Apr 11.

Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Binge-eating disorder is the most prevalent eating disorder diagnosed, affecting three times more women than men. Ghrelin stimulates appetite and reward signaling, and loss of its receptor reduces binge-eating behavior in male mice. Here, we examined the influence of ghrelin itself on binge-eating behavior in both male and female mice. Read More

Am J Physiol Endocrinol Metab 2022 05 4;322(5):E446-E463. Epub 2022 Apr 4.

Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada.

The pancreatic islet is responsive to an array of endocrine, paracrine, and nutritional inputs that adjust hormone secretion to ensure accurate control of glucose homeostasis. Although the mechanisms governing glucose-coupled insulin secretion have received the most attention, there is emerging evidence for a multitude of physiological signaling pathways and paracrine networks that collectively regulate insulin, glucagon, and somatostatin release. Moreover, the modulation of these pathways in conditions of glucotoxicity or lipotoxicity are areas of both growing interest and controversy. Read More

Am J Physiol Endocrinol Metab 2022 05 4;322(5):E464-E466. Epub 2022 Apr 4.

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas.

Am J Physiol Endocrinol Metab 2022 06 4;322(6):E508-E516. Epub 2022 Apr 4.

Department of Medicine, Georgia Prevention Institute, Augusta University, Augusta, Georgia.

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Read More

Am J Physiol Endocrinol Metab 2022 05 28;322(5):E425-E435. Epub 2022 Mar 28.

Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.

A single bout of exercise can potentiate the effect of insulin on skeletal muscle glucose uptake via activation of the AMPK-TBC1 domain family member 4 (TBC1D4) pathway, which suggests a positive correlation between AMPK activation and insulin sensitization. In addition, prolonged fasting in rodents is known to upregulate and thereby synergistically enhance the effect of exercise on muscle AMPK activation. Therefore, fasting may potentiate the insulin-sensitizing effect of exercise. Read More

Am J Physiol Endocrinol Metab 2022 05 28;322(5):E436-E445. Epub 2022 Mar 28.

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

The melanocortin 4 receptor (MC4R) plays an important role in the regulation of appetite and energy expenditure in humans and rodents. Impairment of MC4R signaling causes severe obesity. MC4R mainly couples to the G-protein G. Read More

Am J Physiol Endocrinol Metab 2022 05 14;322(5):E414-E424. Epub 2022 Mar 14.

Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

One anastomosis gastric bypass (OAGB) surgery became a common bariatric procedure in recent years. In this surgery, the distal stomach, duodenum, and proximal jejunum are bypassed, leading to weight loss, improvement in metabolic parameters, and a change in hormonal secretion. We sought to generate and characterize a mouse model for OAGB. Read More

Am J Physiol Endocrinol Metab 2022 Mar;322(3):E330

Am J Physiol Endocrinol Metab 2022 04 28;322(4):E366-E381. Epub 2022 Feb 28.

Centre for Research in Vascular Biology, University College Cork, Cork, Ireland.

This review aims to describe and compare porcine models of metabolic syndrome. This syndrome and its associated secondary comorbidities are set to become the greatest challenge to healthcare providers and policy makers in the coming century. However, an incomplete understanding of the pathogenesis has left significant knowledge gaps in terms of efficacious therapeutics. Read More

Am J Physiol Endocrinol Metab 2022 04 21;322(4):E355-E365. Epub 2022 Feb 21.

Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.

Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation induced by insulin further contributes to increased MSNA via arterial baroreflex-mediated mechanisms requires further investigation. Accordingly, we examined baroreflex modulation of the MSNA response to hyperinsulinemia. Read More

Am J Physiol Endocrinol Metab 2022 Feb;322(2):E197

Am J Physiol Endocrinol Metab 2022 04 14;322(4):E331-E343. Epub 2022 Feb 14.

Department of Biomedical Sciences and Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio.

Fsp27 was previously identified as a lipid droplet-associated protein in adipocytes. Various studies have shown that it plays a role in the regulation of lipid homeostasis in adipose tissue and liver. However, its function in muscle, which also accumulate and metabolize fat, remains completely unknown. Read More

Am J Physiol Endocrinol Metab 2022 04 14;322(4):E344-E354. Epub 2022 Feb 14.

Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

The gut microbiome has the capacity to regulate bone mass. The aim of this study was to develop a nutritional synbiotic dietary assemblage at an optimal dose to maintain bone mass in ovariectomized (Ovx) mice. We performed genomic analyses and in vitro experiments in a large collection of bacterial and fungal strains (>4,000) derived from fresh fruit and vegetables to identify candidates with the synergistic capacity to produce bone-protective short-chain fatty acids (SCFA) and vitamin K2. Read More

Am J Physiol Endocrinol Metab 2022 05 14;322(5):E383-E413. Epub 2022 Feb 14.

Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.

Persistent organic pollutants (POPs) are a diverse family of contaminants that show widespread global dispersion and bioaccumulation. Humans are continuously exposed to POPs through diet, air particles, and household and commercial products; POPs are consistently detected in human tissues, including the pancreas. Epidemiological studies show a modest but consistent correlation between exposure to POPs and increased diabetes risk. Read More

Am J Physiol Endocrinol Metab 2022 03 14;322(3):E319-E329. Epub 2022 Feb 14.

Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands.

DNA damage responses compete for cellular resources with metabolic pathways, but little is known about the metabolic consequences of impaired DNA replication, a process called replication stress. Here we characterized the metabolic consequences of DNA replication stress at endogenous DNA lesions by using mice with a disruption of Rev1, a translesion DNA polymerase specialized in the mutagenic replication of damaged DNA. Male and female Rev1 knockout (KO) mice were compared with wild-type (WT) mice and followed over time to study the natural course of body weight gain and glucose tolerance. Read More

Am J Physiol Endocrinol Metab 2022 03 7;322(3):E293-E306. Epub 2022 Feb 7.

Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia.

Insulin increases muscle microvascular perfusion, which contributes to its metabolic action in muscle, but this action is impaired in obesity. Metformin improves endothelial function beyond its glucose lowering effects. We aim to examine whether metformin could prevent microvascular insulin resistance and endothelial dysfunction during the development of obesity. Read More

Am J Physiol Endocrinol Metab 2022 03 7;322(3):E307-E318. Epub 2022 Feb 7.

Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

Type 2 diabetes is associated with the upregulation of neprilysin, a peptidase capable of cleaving glucoregulatory peptides such as glucagon-like peptide-1 (GLP-1). In humans, use of the neprilysin inhibitor sacubitril in combination with an angiotensin II receptor blocker was associated with increased plasma GLP-1 levels and improved glycemic control. Whether neprilysin inhibition per se is mediating these effects remains unknown. Read More

Am J Physiol Endocrinol Metab 2022 03 24;322(3):E278-E292. Epub 2022 Jan 24.

Cachexia Research Laboratory, Exercise Science Research Center, Department of Human Health Performance and Recreation, University of Arkansas, Fayetteville, Arkansas.

microRNAs (miRs) are linked to various human diseases including type 2 diabetes mellitus (T2DM) and emerging evidence suggests that miRs may serve as potential therapeutic targets. Lower miR-16 content is consistent across different models of T2DM; however, the role of miR-16 in muscle metabolic health is still elusive. Therefore, the purpose of this study was to investigate how deletion of miR-16 in mice affects skeletal muscle metabolic health and contractile function in both sexes. Read More