scEMC10, a novel circulating inhibitor of adipocyte thermogenesis, is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity

2021 ◽  
Author(s):  
Xuanchun Wang ◽  
Guifen Qiang ◽  
YANLIANG LI ◽  
Kaihua Wang ◽  
Jiarong Dai ◽  
...  
Keyword(s):  
Physiological Function ◽  
Neutralizing Antibody ◽  
Endoplasmic Reticulum Membrane ◽  
Secreted Protein ◽  
Obese Mice ◽  
Human Obesity ◽  
Potential Therapeutic Target ◽  
Stimulatory Action ◽  
Membrane Complex ◽  
Diet Induced Obesity

Abstract Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterised secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in humans with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a novel circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.

Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation

2008 ◽  
Vol 104 (6) ◽  
pp. 1727-1735 ◽  
Author(s):  
Richard A. Johnston ◽  
Todd A. Theman ◽  
Frank L. Lu ◽  
Raya D. Terry ◽  
Erin S. Williams ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Pulmonary Inflammation ◽  
Extended Period ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Obese Mice ◽  
Human Obesity ◽  
Diet Induced Obesity ◽  
Inducible Protein ◽  
Fat Diets

We previously reported that genetically obese mice exhibit innate airway hyperresponsiveness (AHR) and enhanced ozone (O3)-induced pulmonary inflammation. Such genetic deficiencies in mice are rare in humans, and they may not be representative of human obesity. Thus the purpose of this study was to determine the pulmonary phenotype of mice with diet-induced obesity (DIO), which more closely mimics the cause of human obesity. Therefore, wild-type C57BL/6 mice were reared from the time of weaning until at least 30 wk of age on diets in which either 10 or 60% of the calories are derived from fat in the form of lard. Body mass was ∼40% greater in mice fed 60 vs. 10% fat diets. Baseline airway responsiveness to intravenous methacholine, measured by forced oscillation, was greater in mice fed 60 vs. 10% fat diets. We also examined lung permeability and inflammation after exposure to room air or O3 (2 parts/million for 3 h), an asthma trigger. Four hours after the exposure ended, O3-induced increases in bronchoalveolar lavage fluid protein, interleukin-6, KC, macrophage inflammatory protein-2, interferon-γ-inducible protein-10, and eotaxin were greater in mice fed 60 vs. 10% fat diets. Innate AHR and augmented responses to O3 were not observed in mice raised from weaning until 20–22 wk of age on a 60% fat diet. These results indicate that mice with DIO exhibit innate AHR and enhanced O3-induced pulmonary inflammation, similar to genetically obese mice. However, mice with DIO must remain obese for an extended period of time before this pulmonary phenotype is observed.

scholarly journals Four-and-a-half LIM domain protein 2 (FHL2) deficiency protects mice from diet-induced obesity and high FHL2 expression marks human obesity

Metabolism ◽  
2021 ◽  
pp. 154815
Author(s):  
Maria P. Clemente-Olivo ◽  
Jayron J. Habibe ◽  
Mariska Vos ◽  
Roelof Ottenhoff ◽  
Aldo Jongejan ◽  
...  
Keyword(s):  
Lim Domain ◽  
Human Obesity ◽  
Diet Induced Obesity ◽  
Lim Domain Protein ◽  
Domain Protein

scholarly journals Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5826-5834 ◽  
Author(s):  
Shoshana Yakar ◽  
Nomeli P. Nunez ◽  
Patricia Pennisi ◽  
Pnina Brodt ◽  
Hui Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tumor Growth ◽  
Glucose Intolerance ◽  
Tumor Development ◽  
Tumor Growth Rate ◽  
Obese Mice ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Obese Female

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

scholarly journals Endospanin 1 Determines the Balance of Leptin-Regulated Hypothalamic Functions

2018 ◽  
Vol 108 (2) ◽  
pp. 132-141
Author(s):  
Clara Roujeau ◽  
Ralf Jockers ◽  
Julie Dam
Keyword(s):  
Signaling Pathways ◽  
Intracellular Trafficking ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Human Obesity ◽  
Leptin Signaling ◽  
Diet Induced Obesity ◽  
Important Regulator ◽  
Neuronal Plasma Membrane ◽  
Underlying Mechanisms

Endospanin 1 (Endo1), a protein encoded in humans by the same gene than the leptin receptor (ObR), and increased by diet-induced obesity, is an important regulator of ObR trafficking and cell surface exposure, determining leptin signaling strength. Defective intracellular trafficking of the leptin receptor to the neuronal plasma membrane has been proposed as a mechanism underlying the development of leptin resistance observed in human obesity. More recently, Endo1 has emerged as a mediator of “selective leptin resistance.” The underlying mechanisms of the latter are not completely understood, but the possibility of differential activation of leptin signaling pathways was suggested among others. In this respect, the expression level of Endo1 is crucial for the appropriate balance between different leptin signaling pathways and leptin functions in the hypothalamus and is likely participating in selective leptin resistance for the control of energy and glucose homeostasis.

scholarly journals White tea (Camellia sinensis) extract reduces oxidative stress and triacylglycerols in obese mice

2012 ◽  
Vol 32 (4) ◽  
pp. 733-741 ◽  
Author(s):  
Lílian Gonçalves Teixeira ◽  
Priscilla Ceci Lages ◽  
Tatianna Lemos Jascolka ◽  
Edenil Costa Aguilar ◽  
Fabíola Lacerda Pires Soares ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Adipose Tissue ◽  
Camellia Sinensis ◽  
Reduce Food Intake ◽  
Obese Mice ◽  
White Tea ◽  
Diet Induced Obesity ◽  
Tea Extract ◽  
The Relationship

White tea is an unfermented tea made from young shoots of Camellia sinensis protected from sunlight to avoid polyphenol degradation. Although its levels of catechins are higher than those of green tea (derived from the same plant), there are no studies addressing the relationship between this tea and obesity associated with oxidative stress.The objective of this study was to evaluate the effect of white tea on obesity and its complications using a diet induced obesity model. Forty male C57BL/6 mice were fed a high-fat diet to induce obesity (Obese group) or the same diet supplemented with 0.5% white tea extract (Obese + WTE) for 8 weeks. Adipose tissue, serum lipid profile, and oxidative stress were studied. White tea supplementation was not able to reduce food intake, body weight, or visceral adiposity. Similarly, there were no changes in cholesterol rich lipoprotein profile between the groups. A reduction in blood triacylglycerols associated with increased cecal lipids was observed in the group fed the diet supplemented with white tea. White tea supplementation also reduced oxidative stress in liver and adipose tissue. In conclusion, white tea extract supplementation (0.5%) does not influence body weight or adiposity in obese mice. Its benefits are restricted to the reduction in oxidative stress associated with obesity and improvement of hypertriacylglycerolemia.

BCAA Supplementation in Mice with Diet-Induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis

Endocrinology ◽  
2021 ◽  
Author(s):  
Jennifer Lee ◽  
Archana Vijayakumar ◽  
Phillip J White ◽  
Yuping Xu ◽  
Olga Ilkayeva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Obese Mice ◽  
High Fat ◽  
Leucine Oxidation ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Chain Acyl ◽  
Branched Chain ◽  
Relationship Of

Abstract Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD-feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and BCKA levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from HFHS or HFD-fed mice, but did not worsen insulin resistance. A set of short and long-chain acyl CoAs were elevated by diet alone in muscle, liver and WAT, but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on two different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.

Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1

2020 ◽  
Vol 11 (3) ◽  
pp. 2418-2426 ◽  
Author(s):  
Mailin Gan ◽  
Linyuan Shen ◽  
Shujie Wang ◽  
Zhixian Guo ◽  
Ting Zheng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Target Genes ◽  
Obese Mice ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Regulate Lipid Metabolism

Genistein may regulate lipid metabolism in adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1.

scholarly journals Obesity Augments Glucocorticoid-Dependent Muscle Atrophy in Male C57BL/6J Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 420
Author(s):  
Laura C. Gunder ◽  
Innocence Harvey ◽  
JeAnna R. Redd ◽  
Carol S. Davis ◽  
Ayat AL-Tamimi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Muscle Atrophy ◽  
Lean Mass ◽  
Muscle Fibers ◽  
Muscle Size ◽  
Type Ii ◽  
Obese Mice ◽  
Diet Induced Obesity ◽  
Synthetic Glucocorticoid

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together, these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

A metagenomics approach to the intestinal microbiome structure and function in high fat diet-induced obesity mice fed with oolong tea polyphenols

2018 ◽  
Vol 9 (2) ◽  
pp. 1079-1087 ◽  
Author(s):  
Mei Cheng ◽  
Xin Zhang ◽  
Jieyu Zhu ◽  
Lu Cheng ◽  
Jinxuan Cao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Structure And Function ◽  
Tea Polyphenols ◽  
Intestinal Microbiome ◽  
Obese Mice ◽  
High Fat ◽  
Oolong Tea ◽  
Diet Induced Obesity ◽  
And Function ◽  
Human Flora

We investigate the modulatory effect of oolong tea polyphenols on the intestinal microbiota in human flora-associated high fat diet induced obese mice.

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