Article
|
Open Access
Featured
-
-
Article
| Open Access
MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis
The hypothalamus controls systemic energy homeostasis. Here, the authors show that loss of microRNA-7 in hypothalamic neurons causes obesity, increased growth and endocrine dysfunction in mice, and report genetic evidence that links microRNA-7 to height and adiposity in humans.
- Mary P. LaPierre
- , Katherine Lawler
- & Markus Stoffel
-
Article
| Open Access
Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity
Murine models of obesity suggest that decreases in the adipose tissue regulatory T cell compartment may contribute to insulin resistance, but how this corresponds in the human clinical context is less well understood. Here the authors propose a role for interferon gamma in shrinking the adipose tissue regulatory T cell compartment seen in human obesity and assess the alterations seen during induction of dietary changes.
- David Bradley
- , Alan J. Smith
- & Willa A. Hsueh
-
Article
| Open Access
No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial
Exercise modulates brown adipose tissue (BAT) metabolism in murine models. Here the authors report that there is no evidence that 24 weeks of supervised exercise training modulates BAT volume or function in young sedentary adults in the ACTIBATE randomized controlled trial.
- Borja Martinez-Tellez
- , Guillermo Sanchez-Delgado
- & Jonatan R. Ruiz
-
Article
| Open Access
Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase
Energy metabolism is dysregulated in obesity, and some if these changes persist after weight loss and may contribute to weight regain. Here the authors report that a vacuolar-type H+ ATPase, ATP6v0a1, is induced in adipocytes during obesity and persists after weight loss, and regulates food intake and weight gain in C. elegans and mice.
- Rizaldy C. Zapata
- , Maria Carretero
- & Olivia Osborn
-
Article
| Open Access
Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling
Interferon Regulatory Factor 5 levels have been shown to increase in adipose tissue macrophages in diet-induced obesity. Here authors show that IRF5 transcriptionally represses the Growth Hormone Inducible Transmembrane Protein gene encoding a mitochondrial protein important for oxidative respiration in macrophages, thus driving the detrimental metabolic changes observed in obesity.
- L. Orliaguet
- , T. Ejlalmanesh
- & F. Alzaid
-
Article
| Open Access
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes
Fat distribution is associated with cardiometabolic disease, although it has been less well studied than overall obesity. In a multiancestry exome-sequencing study, the authors identified predicted loss-of-function mutations in INHBE associated with favorable fat distribution and protection from type 2 diabetes.
- Parsa Akbari
- , Olukayode A. Sosina
- & Luca A. Lotta
-
Article
| Open Access
Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment
Weight regain after weight loss is a challenge in obesity treatment and may involve altered eating and sedentary behaviour after weight loss. Here the authors report an exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment.
- Simon Birk Kjær Jensen
- , Charlotte Janus
- & Signe Sørensen Torekov
-
Article
| Open Access
Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing
Defective insulin secretion is observed early in the development of diabetes. Here the authors report that β cell-specific deficiency of the insulin prohormone convertase 1/3 (PC1/3) leads not only to hyperglycemia, but also to hyperphagic obesity in mice.
- Daniel T. Meier
- , Leila Rachid
- & Marc Y. Donath
-
Article
| Open Access
EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance
In obesity, adipose tissue is chronically inflamed, leading to insulin resistance, and adipose tissue macrophages (ATMs) are a major source of cytokines that aggravate adipocyte dysfunction. Here, the authors show that selective deletion of the epidermal growth factor receptor in ATMs decreased obesity and development of insulin resistance.
- Shirong Cao
- , Yu Pan
- & Ming-Zhi Zhang
-
Article
| Open Access
Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity
Abdominal fat has been shown to increase cardiometabolic disease risk. In this study, the authors report that loss-of-function variants in the gene INHBE associate with lower BMI-adjusted waist-to-hip ratio, a surrogate measure of abdominal fat.
- Aimee M. Deaton
- , Aditi Dubey
- & Paul Nioi
-
Article
| Open Access
Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism
Dysregulation of plasmalogen metabolism in adipose tissue is associated with metabolic diseases. Here the authors characterize the role of adipocyte TMEM86A as a lysoplasmalogenase and show its deletion is protective against high fat diet induced metabolic disease, an effect that can be recapitulated by plasmenyl lysophosphatidylethanolamine 18:0 supplementation.
- Yoon Keun Cho
- , Young Cheol Yoon
- & Yun-Hee Lee
-
Article
| Open Access
Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
The inherited basis of body fat distribution is not fully understood. Here, the authors use genetic data and MRI-derived measures of local adiposity to highlight fat depot-specific genetic architecture with implications for cardiometabolic health.
- Saaket Agrawal
- , Minxian Wang
- & Amit V. Khera
-
Article
| Open Access
Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
Here, the authors characterize gut viromes in a cohort of individuals with metabolic syndrome, which they find associated with a highly widespread family of gut bacteriophages they name Candidatus Heliusviridae.
- Patrick A. de Jonge
- , Koen Wortelboer
- & Hilde Herrema
-
Article
| Open Access
Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling
Kynurenine, a tryptophan metabolite, is increased in the circulating plasma of obese individuals, but the source has been unclear. Here, the authors show in mice that mature adipocytes produce kynurenine, with vitamin B6 administration preventing accumulation and protecting against high-fat diet.
- Teng Huang
- , Jia Song
- & Cong-Yi Wang
-
Article
| Open Access
Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation
Thyroid hormone (TH) action regulates brown adipose tissue thermogenic capacity through incompletely understood mechanisms. Here the authors report that T3, the active form of TH, increases thermogenic capacity via thyroid hormone receptor α-mediated hyperplasia of brown adipose tissue adipocyte progenitor cells.
- Shengnan Liu
- , Siyi Shen
- & Hao Ying
-
Article
| Open Access
Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice
Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity.
- Shaojian Lin
- , Anke Zhang
- & Bing Luan
-
Article
| Open Access
Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice
Adipose immune cells contribute to obesity-related disease, but less is known about weight cycling. Here, authors show that weight loss reduces diabetes risk, but inflammatory adipose immune cell populations persist and may contribute to worsened diabetes risk upon weight regain.
- Matthew A. Cottam
- , Heather L. Caslin
- & Alyssa H. Hasty
-
Article
| Open Access
The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase
Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.
- Alastair G. Kerr
- , Zuoneng Wang
- & Hui Gao
-
Article
| Open Access
Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration
Impaired mitochondrial function in liver tissue may contribute to the pathogenesis and disease progression of nonalcoholic fatty liver disease (NAFLD). Here the authors report that patients with obesity have lower mitochondrial capacity in adipose tissues but higher capacity in the liver, without overall associations to NAFLD severity, and that bariatric surgery increases hepatic mitochondrial respiration and mitochondrial biogenesis.
- Julie S. Pedersen
- , Marte O. Rygg
- & Flemming Dela
-
Article
| Open Access
IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice
TLRs/IL-1R signaling play a role in high-fat diet induced adipose tissue dysfunction and obesity-associated metabolic syndrome. Here the authors report that adipocyte-specific deficiency of IL-1 Receptor-Associated Kinase M (IRAKM) ameliorates diet induced obesity, potentially via the mitochondrial citrate carrier Slc25a1 and reduced de novo lipogenesis.
- Weiwei Liu
- , Hao Zhou
- & Xiaoxia Li
-
Article
| Open Access
DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.
- Matthias Wielscher
- , Pooja R. Mandaviya
- & Marjo-Riitta Järvelin
-
Article
| Open Access
Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice
Caloric restriction is a common approach to weight reduction, however, weight regain is common. Here the authors report that caloric restriction reduces the abundance of Parabacteroides distasonis in the gut and alters serum bile acid (BA) profile, which contribute to weight regain in mice.
- Mengci Li
- , Shouli Wang
- & Wei Jia
-
Article
| Open Access
Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice
Senescent cells play a role in pathogenesis of diabetes, and senolytic agents can improve obesity- and diabetes-related pathologies. Here the authors report that mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, alleviates symptoms of obesity and prediabetes in mice, potentially via reduction of food intake and elimination of senescent cells.
- Eliska Vacurova
- , Jaroslava Trnovska
- & Jiri Neuzil
-
Article
| Open Access
Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice
Yogurt consumption is associated with health benefits, but underlying mechanisms are unknown. Here, the authors show in a mouse model that yogurt intake prevents obesity-linked insulin resistance and hepatic steatosis through shifting the gut microbiota and enhancing production of fermentation-derived branched chain hydroxy acids.
- Noëmie Daniel
- , Renato Tadeu Nachbar
- & André Marette
-
Article
| Open Access
Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis
High methionine and S-adenosylmethionine serum levels are related with obesity. Here the authors show that knockdown of methionine adenosyltransferase by using antisense oligonucleotides provides beneficial effects in obesity and comorbidities.
- Diego Sáenz de Urturi
- , Xabier Buqué
- & Patricia Aspichueta
-
Article
| Open Access
Randomized controlled trial for time-restricted eating in healthy volunteers without obesity
Time-restricted eating, both early (eTRF) and mid-day (mTRF), have been shown to have metabolic benefits. Here the authors report a randomized controlled trial to compare the effects of eTRF and mTRF in healthy volunteers without obesity, and find that eTRF is more effective in improving the primary outcome insulin sensitivity.
- Zhibo Xie
- , Yuning Sun
- & Yilei Mao
-
Article
| Open Access
Pharmacologic IRE1/XBP1s activation promotes systemic adaptive remodeling in obesity
Signalling through the IRE1 arm of the unfolded protein response exerts both protective and harmful effects in obesity. Here the authors report that a selective pharmacologic activator of IRE1/XBP1s signalling stimulates an adaptive remodelling of liver and pancreas in diet-induced obese mice and mitigates obesity-linked systemic metabolic dysfunction.
- Aparajita Madhavan
- , Bernard P. Kok
- & R. Luke Wiseman
-
Article
| Open Access
Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Bingyang Dai
- , Jiankun Xu
- & Ling Qin
-
Article
| Open Access
The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage
HNF4A is a nuclear receptor that regulates liver lipid homeostasis. Here the authors show that HNF4A is not required for intestinal lipid metabolism but controls energy expenditure under diet induced obesity through the fat-induced release of glucose-dependent insulinotropic polypeptide.
- Romain Girard
- , Sarah Tremblay
- & François Boudreau
-
Article
| Open Access
Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition
Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.
- Rebecca Rimbach
- , Yosuke Yamada
- & John R. Speakman
-
Article
| Open Access
The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes
The p53 tumor suppressor is also a regulator of metabolism, but the mechanisms controlling p53-associated metabolic activities remain poorly understood. Here the authors report that the deletion of the multifunctional protein E4F1 is protective against diet-induced obesity in mice, and E4F1 regulates adipocyte lipid metabolism through p53.
- Matthieu Lacroix
- , Laetitia K. Linares
- & Laurent Le Cam
-
Article
| Open Access
Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα
Intestinal surface changes in size and function, but what propels these alterations is unknown. Here, the authors show that food excess increases the gut absorptive capacity, and that in presence of dietary lipids, intestinal PPARα is indispensable for the adaptive increase in villi length and function.
- Ozren Stojanović
- , Jordi Altirriba
- & Mirko Trajkovski
-
Article
| Open Access
Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.
- Yan-Ting Chen
- , Qi-Yuan Yang
- & Min Du
-
Article
| Open Access
Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat
Brown adipocytes contribute to energy balance, and adipocyte development and brown adipocyte thermogenesis are in part regulated by epigenetic modifications. Here the authors report that the histone demethylase Utx maintains brown adipocyte identity via demethylation of PRDM16, which in turn represses myogenic remodelling via DNMT1-mediated Myod1 promoter hypermethylation in mice.
- Fenfen Li
- , Jia Jing
- & Bingzhong Xue
-
Article
| Open Access
The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages
Inflammasome regulation is not fully understood. Here the authors show that the early endosomal APPL1-Rab5 axis removes damaged mitochondria and then restricts the inflammasome response in macrophages, alleviating the inflammatory diseases.
- Kelvin Ka Lok Wu
- , KeKao Long
- & Kenneth King Yip Cheng
-
Article
| Open Access
Diet composition influences the metabolic benefits of short cycles of very low caloric intake
Understanding the contribution of diet composition, calories and length of fasting in health maintenance is still challenging. Here the authors compare the effects of cycles of intermittent very low calorie intake achieved with a plant-based fasting mimicking diet or standard laboratory chow to provide insights into the role played by diet composition in mediating the metabolic benefits of short cycles of very low-calorie intake in mice.
- Alberto Diaz-Ruiz
- , Tyler Rhinesmith
- & Rafael de Cabo
-
Article
| Open Access
Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice
Misregulation of chromatin has been linked to many conditions, including obesity, but the details remain unclear. Here the authors identify the H4 lysine 16 acetyltransferase MOF as a master regulator of glucose metabolism that is required for normal glucose uptake and fat storage.
- Cecilia Pessoa Rodrigues
- , Aindrila Chatterjee
- & Asifa Akhtar
-
Article
| Open Access
Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue
Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.
- Xin Cui
- , Jia Jing
- & Hang Shi
-
Article
| Open Access
Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding
Tissue circadian clocks contribute to the regulation of physiology and metabolism. Here the authors investigate the role of the intestinal circadian clock in energy homeostasis and show that the intestinal clock acts as an accelerator in dietary fat absorption.
- Fangjun Yu
- , Zhigang Wang
- & Baojian Wu
-
Article
| Open Access
A functional genomics pipeline identifies pleiotropy and cross-tissue effects within obesity-associated GWAS loci
Many genetic loci have been linked to obesity, but knowledge of their functional mechanisms is limited. Here, the authors perform reporter assays and temporal functional genomics data generation to characterize obesity genetic loci and find that loci often harbor multiple functional variants.
- Amelia C. Joslin
- , Débora R. Sobreira
- & Marcelo A. Nóbrega
-
Article
| Open Access
Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity
The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here the authors report that inactivation of the orexin receptor type 1 or 2 in serotonergic neurons differentially regulate systemic glucose homeostasis in the context of diet induced obesity.
- Xing Xiao
- , Gagik Yeghiazaryan
- & A. Christine Hausen
-
Article
| Open Access
NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity
Calcitonin receptor-expressing neurons of the nucleus tractus solitarius contribute to long-term control of food intake and body weight. The authors show that a subset of these cells expresses Prlh and that enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity in mice.
- Wenwen Cheng
- , Ermelinda Ndoka
- & Martin G. Myers Jr
-
Article
| Open Access
The pesticide chlorpyrifos promotes obesity by inhibiting diet-induced thermogenesis in brown adipose tissue
Chlorpyrifos is a widely-used pesticide and a common residue on vegetables and fruits. Here the authors show that at non-neurotoxic doses, chlorpyrifos reduces energy expenditure, by inhibiting diet induced thermogenesis, and promotes obesity and insulin resistance.
- Bo Wang
- , Evangelia E. Tsakiridis
- & Gregory R. Steinberg
-
Article
| Open Access
Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
Hyaluronan is a naturally occurring linear polysaccharide that together with collagens, enzymes, and glycoproteins forms the extracellular matrix. Here the authors show that adipose tissue overproduction of Hyaluronan reduces fat accumulation in mice fed high-fat diet and improves systemic glucose homeostasis.
- Yi Zhu
- , Na Li
- & Philipp E. Scherer
-
Article
| Open Access
Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice
The mechanisms that mediate the effects of weight loss surgeries such as vertical sleeve gastrectomy (VSG) are incompletely understood. Here the authors show that intestinal FGF15 is necessary to improve glucose tolerance and to prevent the loss of muscle and bone mass after VSG, potentially via protection against bile acid toxicity.
- Nadejda Bozadjieva-Kramer
- , Jae Hoon Shin
- & Randy J. Seeley
-
Article
| Open Access
Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.
- Allison L. Fisher
- , Veena Sangkhae
- & Elizabeta Nemeth
-
Article
| Open Access
The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice
Beta-cell function is often impaired in obesity through incompletely understood mechanisms. Here the authors show that the long noncoding RNA βFaar is reduced by diet-induced obesity in mice, which leads to impaired beta-cell function via miR-138-5p and survival via TRAF3 Interacting Protein 2.
- Fangfang Zhang
- , Yue Yang
- & Liang Jin
-
Article
| Open Access
Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue
During the expansion of adipose tissue adipocyte progenitor cells proliferate and undergo adipogenesis. Here, the authors show that adipocyte progenitor cell proliferation in visceral adipose tissue has a diurnal pattern, which is dependent on both energy intake and the circadian clock.
- Aleix Ribas-Latre
- , Rafael Bravo Santos
- & Kristin L. Eckel-Mahan
-
Article
| Open Access
Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells
Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.
- Vincenza Cifarelli
- , Sila Appak-Baskoy
- & Nada A. Abumrad
SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner