394 results match your criteria deletion pomc

Hypothalamic steroid receptor coactivator-2 regulates adaptations to fasting and overnutrition.

Cell Rep 2021 Dec;37(10):110075

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address:

The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. Read More

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December 2021

PHIP gene variants with protein modeling, interactions, and clinical phenotypes.

Am J Med Genet A 2022 Feb 13;188(2):579-589. Epub 2021 Nov 13.

Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA.

Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic features, cognitive dysfunction, aberrant behavior, and childhood onset obesity. Following a systematic literature review, 35 patients are reported to have unique PHIP variants impacting the encoded protein product. We summarize the status and frequency of these variants and relationship to clinical presentation. Read More

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February 2022

Deletion of in Hypothalamic Arcuate Nucleus Kiss1 Neurons Potentiates Synchronous GCaMP Activity and Protects against Diet-Induced Obesity.

J Neurosci 2021 11 15;41(47):9688-9701. Epub 2021 Oct 15.

Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon 97239

Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. High-frequency firing of hypothalamic arcuate Kiss1 (Kiss1) neurons releases kisspeptin into the median eminence, and neurokinin B (NKB) and dynorphin onto neighboring Kiss1 neurons to generate a slow EPSP mediated by TRPC5 channels that entrains intermittent, synchronous firing of Kiss1 neurons. High-frequency optogenetic stimulation of Kiss1 neurons also releases glutamate to excite the anorexigenic proopiomelanocortin (POMC) neurons and inhibit the orexigenic neuropeptide Y/agouti-related peptide (AgRP) neurons via metabotropic glutamate receptors. Read More

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November 2021

Genetic Deletion of KLHL1 Leads to Hyperexcitability in Hypothalamic POMC Neurons and Lack of Electrical Responses to Leptin.

Front Neurosci 2021 9;15:718464. Epub 2021 Sep 9.

Cell and Molecular Physiology Department and Neuroscience Division of the Cardiovascular Research Institute, Loyola University Chicago, Maywood, IL, United States.

Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage-gated calcium channels. The KLHL1 knockout (KO) model displays altered calcium channel expression in various brain regions. We analyzed the electrical behavior of hypothalamic POMC (proopiomelanocortin) neurons and their response to leptin. Read More

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September 2021

Deletion of the Feeding-Induced Hepatokine TSK Ameliorates the Melanocortin Obesity Syndrome.

Diabetes 2021 09 28;70(9):2081-2091. Epub 2021 Jun 28.

Life Sciences Institute and Department of Cell & Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, MI

Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a leucine-rich repeat-containing protein secreted primarily by the liver that exerts an inhibitory effect on brown fat sympathetic innervation and thermogenesis. Despite this, physiological regulation of TSK and the mechanisms underlying its effects on energy balance remain poorly understood. Read More

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September 2021

Cellular carbon stress is a mediator of obesity-associated osteoarthritis development.

Osteoarthritis Cartilage 2021 09 10;29(9):1346-1350. Epub 2021 May 10.

Department of Biomedical Sciences, Ohio University, OH, 45701, USA; Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, OH, 45701, USA. Electronic address:

Objective: 'Carbon stress' is a newly found mechanism that links obesity and dysregulated metabolism. It is defined as the cellular accumulation of metabolites during obesity post-translationally modifying metabolic proteins and decreasing their enzymatic activity. The objective of this study was to investigate if 'carbon stress' also occurs in cartilage and contributes to obesity associated OA development. Read More

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September 2021

Hypothalamic GHR-SIRT1 Axis in Fasting.

Cells 2021 04 14;10(4). Epub 2021 Apr 14.

Department of Biological Sciences, Integrative Biosciences Center (IBio), Wayne State University, Detroit, Michigan, MI 48202, USA.

Many aspects of physiological functions are controlled by the hypothalamus, a brain region that connects the neuroendocrine system to whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions known to participate in the regulation of feeding and whole-body energy homeostasis. Sirtuin 1 (SIRT1) is the most conserved mamma-lian nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase that plays a key role in controlling life span and sensing nutrient availability in the hypothalamus in response to caloric restriction. Read More

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AgRP signalling negatively regulates bone mass.

J Neuroendocrinol 2021 Apr 29;33(5):e12978. Epub 2021 Apr 29.

Eating Disorders Group, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.

The central nervous system is an active and major regulator of bone structure and remodelling. Specifically, signalling within the hypothalamus has been shown to be critical to ensuring that skeletal functions align with whole body metabolic supply and demand. Here, we identify agouti-related peptide (AgRP), an orexigenic peptide exclusively co-expressed with neuropeptide Y (NPY) in the arcuate nucleus (ARC) of the hypothalamus, as another critical player in the central control of bone homeostasis. Read More

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Mice lacking PC1/3 expression in POMC-expressing cells do not develop obesity.

Endocrinology 2021 Mar 10. Epub 2021 Mar 10.

Department of Anatomy and Neurobiology, University of Maryland-Baltimore, Baltimore, MD.

Pro-opiomelanocortin (POMC) neurons form an integral part of the central melanocortin system regulating food intake and energy expenditure. Genetic and pharmacological studies have revealed that defects in POMC synthesis, processing, and receptor signaling lead to obesity. It is well established that POMC is extensively processed by a series of enzymes, including prohormone convertases PC1/3 and PC2, and that genetic insufficiency of both PC1/3 and POMC is strongly associated with obesity risk. Read More

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β-endorphin differentially contributes to food anticipatory activity in male and female mice undergoing activity-based anorexia.

Physiol Rep 2021 03;9(5):e14788

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.

Anorexia nervosa (AN) has a lifetime prevalence of up to 4% and a high mortality rate (~5-10%), yet little is known regarding the etiology of this disease. In an attempt to fill the gaps in knowledge, activity-based anorexia (ABA) in rodents has been a widely used model as it mimics several key features of AN including severely restricted food intake and excessive exercise. Using this model, a role for the hypothalamic proopiomelanocortin (POMC) system has been implicated in the development of ABA as Pomc mRNA is elevated in female rats undergoing the ABA paradigm. Read More

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Rare deleterious germline variants and risk of lung cancer.

NPJ Precis Oncol 2021 Feb 16;5(1):12. Epub 2021 Feb 16.

Mayo Clinic College of Medicine, Scottsdale, AZ, USA.

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Read More

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February 2021

Sirtuin 6 supra-physiological overexpression in hypothalamic pro-opiomelanocortin neurons promotes obesity via the hypothalamus-adipose axis.

FASEB J 2021 03;35(3):e21408

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital of Sichuan University, Chengdu, China.

Sirtuin 6 (Sirt6), a member of the Sirtuin family, has important roles in maintaining glucose and lipid metabolism. Our previous studies demonstrated that the deletion of Sirt6 in pro-opiomelanocortin (POMC)-expressing cells by the loxP-Cre system resulted in severe obesity and hepatic steatosis. However, whether overexpression of Sirt6 in hypothalamic POMC neurons could ameliorate diet-induced obesity is still unknown. Read More

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Energy state alters regulation of proopiomelanocortin neurons by glutamatergic ventromedial hypothalamus neurons: pre- and postsynaptic mechanisms.

J Neurophysiol 2021 03 13;125(3):720-730. Epub 2021 Jan 13.

Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.

To maintain metabolic homeostasis, motivated behaviors are driven by neuronal circuits that process information encoding the animal's energy state. Such circuits likely include ventromedial hypothalamus (VMH) glutamatergic neurons that project throughout the brain to drive food intake and energy expenditure. Targets of VMH glutamatergic neurons include proopiomelanocortin (POMC) neurons in the arcuate nucleus that, when activated, inhibit food intake. Read More

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Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer.

PLoS One 2020 31;15(12):e0244793. Epub 2020 Dec 31.

Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus. Read More

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A phosphodiesterase 11 (Pde11a) knockout mouse expressed functional but reduced Pde11a: Phenotype and impact on adrenocortical function.

Mol Cell Endocrinol 2021 01 27;520:111071. Epub 2020 Oct 27.

Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. Electronic address:

Phosphodiesterases catalyze the hydrolysis of cyclic nucleotides and maintain physiologic levels of intracellular concentrations of cyclic adenosine and guanosine mono-phosphate (cAMP and cGMP, respectively). Increased cAMP signaling has been associated with adrenocortical tumors and Cushing syndrome. Genetic defects in phosphodiesterase 11A (PDE11A) may lead to increased cAMP signaling and have been found to predispose to the development of adrenocortical, prostate, and testicular tumors. Read More

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January 2021

PGC-1β-expressing POMC neurons mediate the effect of leptin on thermoregulation in the mouse.

Sci Rep 2020 10 15;10(1):16888. Epub 2020 Oct 15.

Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.

The arcuate nucleus (ARC) of the hypothalamus is a key regulator of food intake, brown adipose tissue (BAT) thermogenesis, and locomotor activity. Whole-body deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1β) disrupts mouse circadian locomotor activity and BAT-regulated thermogenesis, in association with altered gene expression at the central level. We examined whether PGC-1β expression in the ARC is required for proper energy balance and locomotor behavior by generating mice lacking the PGC-1β gene specifically in pro-opiomelanocortin (POMC) neurons. Read More

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October 2020

TPH2 in the Dorsal Raphe Nuclei Regulates Energy Balance in a Sex-Dependent Manner.

Endocrinology 2021 01;162(1)

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas.

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. Read More

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January 2021

Overexpression of Smad7 in hypothalamic POMC neurons disrupts glucose balance by attenuating central insulin signaling.

Mol Metab 2020 12 22;42:101084. Epub 2020 Sep 22.

CAS Key Laboratory of Nutrition, Metabolism and Food safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences. Electronic address:

Objective: Although the hypothalamus is crucial for peripheral metabolism control, the signals in specific neurons involved remain poorly understood. The aim of our current study was to explore the role of the hypothalamic gene mothers against decapentaplegic homolog 7 (Smad7) in peripheral glucose disorders.

Methods: We studied glucose metabolism in high-fat diet (HFD)-fed mice and middle-aged mice with Cre-mediated recombination causing 1) overexpression of Smad7 in hypothalamic proopiomelanocortin (POMC) neurons, 2) deletion of Smad7 in POMC neurons, and 3) overexpression of protein kinase B (AKT) in arcuate nucleus (ARC) in Smad7 overexpressed mice. Read More

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December 2020

Disruption of GABA or glutamate release from POMC neurons in the adult mouse does not affect metabolic end points.

Am J Physiol Regul Integr Comp Physiol 2020 11 16;319(5):R592-R601. Epub 2020 Sep 16.

Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.

Proopiomelanocortin (POMC) neurons contribute to the regulation of many physiological processes; the majority of which have been attributed to the release of peptides produced from the POMC prohormone such as α-MSH, which plays key roles in food intake and metabolism. However, it is now clear that POMC neurons also release amino acid transmitters that likely contribute to the overall function of POMC cells. Recent work indicates that constitutive deletion of these transmitters can affect metabolic phenotypes, but also that the expression of GABAergic or glutamatergic markers changes throughout development. Read More

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November 2020

Leptin, Obesity, and Hypertension: A Review of Pathogenetic Mechanisms.

Metab Syndr Relat Disord 2020 11 1;18(9):399-405. Epub 2020 Sep 1.

Department of Medical Sciences, Frank H. Netter School of Medicine, NH-MED, Quinnipiac University, Hamden, Connecticut, USA.

The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. Read More

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November 2020

Heme attenuates beta-endorphin levels in leukocytes of HIV positive individuals with chronic widespread pain.

Redox Biol 2020 09 13;36:101684. Epub 2020 Aug 13.

Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, USA.

The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. Read More

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September 2020

Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone.

Life Sci 2020 Oct 8;259:118229. Epub 2020 Aug 8.

Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofisica, Sao Paulo 05508-000, Brazil. Electronic address:

Aims: Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells.

Main Methods: Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. Read More

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October 2020

Intestinal NAPE-PLD contributes to short-term regulation of food intake via gut-to-brain axis.

Am J Physiol Endocrinol Metab 2020 09 10;319(3):E647-E657. Epub 2020 Aug 10.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Bruxelles, Belgium.

Our objective was to explore the physiological role of the intestinal endocannabinoids in the regulation of appetite upon short-term exposure to high-fat-diet (HFD) and understand the mechanisms responsible for aberrant gut-brain signaling leading to hyperphagia in mice lacking in the intestinal epithelial cells (IECs). We generated a murine model harboring an inducible NAPE-PLD deletion in IECs (). After an overnight fast, we exposed wild-type (WT) and mice to different forms of lipid challenge (HFD or gavage), and we compared the modification occurring in the hypothalamus, in the vagus nerve, and at endocrine level 30 and 60 min after the stimulation. Read More

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September 2020

Deletion of liver kinase B1 in POMC neurons predisposes to diet-induced obesity.

Life Sci 2020 Oct 5;258:118204. Epub 2020 Aug 5.

Department of Clinical Laboratory Diagnostics, Tianjin Medical University, Tianjin 300203, China; Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Aims: Liver kinase B1 (LKB1) is a serine/threonine kinase. Although many biological functions of LKB1 have been identified, the role of hypothalamic LKB1 in the regulation of central energy metabolism and susceptibility to obesity is unknown. Therefore, we constructed POMC neuron-specific LKB1 knockout mice (PomcLkb1 KO) and studied it at the physiological, morphological, and molecular biology levels. Read More

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October 2020

Regulation of pro-opiomelanocortin (POMC) gene transcription by interleukin-31 via early growth response 1 (EGR-1) in HaCaT keratinocytes.

Mol Biol Rep 2020 Aug 23;47(8):5953-5962. Epub 2020 Jul 23.

Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul, 05029, Republic of Korea.

Pro-opiomelanocortin (POMC) is a large precursor protein of and β-endorphin. POMC expressed in keratinocytes regulates various pathophysiological responses, such as pruritus in atopic dermatitis. Interleukin (IL)-31 is a T helper 2 (Th2)-derived cytokine that functions as a pruritogen, stimulating the sensory neurons in the skin. Read More

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A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue.

Nature 2020 07 22;583(7818):839-844. Epub 2020 Jul 22.

Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.

Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity, and defects in thermogenesis and lipolysis, both of which are adipose tissue functions regulated by the sympathetic nervous system. However, the basis of these sympathetic-associated abnormalities remains unclear. Furthermore, chronic leptin administration reverses these abnormalities in adipose tissue, but the underlying mechanism remains to be discovered. Read More

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Short-term exposure to air pollution (PM) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.

Sci Rep 2020 06 23;10(1):10160. Epub 2020 Jun 23.

School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil.

A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 μm (PM) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding. Read More

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Brain-specific deletion of TRIM13 promotes metabolic stress-triggered insulin resistance, glucose intolerance, and neuroinflammation.

Biochem Biophys Res Commun 2020 06 28;527(1):138-145. Epub 2020 Apr 28.

Department of Geriatric, The First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, 116011, China. Electronic address:

Diabetes has been associated with metabolic disorder, insulin resistance and neuroinflammation. However, the pathogenesis for HFD-induced injury of central nervous system (CNS) is still unclear. Tripartite Motif Containing 13 (TRIM13), also known as RFP2, is a member of TRIM proteins, and is associated with multiple cellular processes, such as apoptosis, survival and inflammation. Read More

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The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates.

Nat Commun 2020 04 20;11(1):1914. Epub 2020 Apr 20.

Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, UMR-S 1172, 59000, Lille, France.

Obesity is associated with the activation of cellular responses, such as endoplasmic reticulum (ER) stress. Here, we show that leptin-deficient ob/ob mice display elevated hypothalamic ER stress as early as postnatal day 10, i.e. Read More

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Hypothalamic POMC deficiency increases circulating adiponectin despite obesity.

Mol Metab 2020 05 7;35:100957. Epub 2020 Feb 7.

Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48105, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA.

Objective: The steep rise in the prevalence of obesity and its related metabolic syndrome have become a major worldwide health concerns. Melanocortin peptides from hypothalamic arcuate nucleus (Arc) POMC neurons induce satiety to limit food intake. Consequently, Arc Pomc-deficient mice (ArcPomc) exhibit hyperphagia and obesity. Read More

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