scholarly journals Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria A. Gonzalez Porras ◽  
Katerina Stojkova ◽  
Marcella K. Vaicik ◽  
Amanda Pelowe ◽  
Anna Goddi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Matrix Composition ◽  
Protein Levels ◽  
Brown Adipose ◽  
Liquid Chromatography Tandem Mass ◽  
Enhanced Expression ◽  
Beige Fat ◽  
Thermogenic Capacity

AbstractObesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis.

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

2015 ◽  
Vol 309 (8) ◽  
pp. E691-E714 ◽  
Author(s):  
Amaia Rodríguez ◽  
Silvia Ezquerro ◽  
Leire Méndez-Giménez ◽  
Sara Becerril ◽  
Gema Frühbeck
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Glucose Disposal ◽  
Cytokine Signaling ◽  
Matrix Remodeling ◽  
Nonalcoholic Fatty Liver ◽  
Brown Adipose ◽  
Wide Range ◽  
Beige Fat

Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases.

scholarly journals Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

2020 ◽  
Vol 12 (2) ◽  
pp. 85-101
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Common Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Brown Adipose ◽  
Key Factor ◽  
Beige Fat

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

scholarly journals Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-13C]Pyruvate MRI in Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2597 ◽  
Author(s):  
Mette Riis-Vestergaard ◽  
Peter Breining ◽  
Steen Pedersen ◽  
Christoffer Laustsen ◽  
Hans Stødkilde-Jørgensen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Fdg Pet ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Protein Levels ◽  
Positron Emission ◽  
Brown Adipose

The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3–4 fold (p < 0.05) as measured by UCP1 gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.

White and beige adipocytes: are they metabolically distinct?

2018 ◽  
Vol 33 (2) ◽  
Author(s):  
Diane M. Sepa-Kishi ◽  
Rolando B. Ceddia
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Adrenergic Stimulation ◽  
Mitochondrial Uncoupling ◽  
Total Body Mass ◽  
Metabolic Characteristics ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Thermogenic Capacity

AbstractThe white adipose tissue (WAT) exhibits great plasticity and can undergo “browning” and acquire features of the brown adipose tissue (BAT), which takes place following cold exposure, chronic endurance exercise or β3-adrenergic stimulation. WAT that underwent browning is characterized by the presence of “beige” adipocytes, which are morphologically similar to brown adipocytes, express uncoupling protein 1 (UCP1) and are considered thermogenically competent. Thus, inducing a BAT-like phenotype in the WAT could promote energy dissipation within this depot, reducing the availability of substrate that would otherwise be stored in the WAT. Importantly, BAT in humans only represents a small proportion of total body mass, which limits the thermogenic capacity of this tissue. Therefore, browning of the WAT could significantly expand the energy-dissipating capacity of the organism and be of therapeutic value in the treatment of metabolic diseases. However, the question remains as to whether WAT indeed changes its metabolic profile from an essentially fat storage/release compartment to an energy dissipating compartment that functions much like BAT. Here, we discuss the differences with respect to thermogenic capacity and metabolic characteristics between white and beige adipocytes to determine whether the latter cells indeed significantly enhance their capacity to dissipate energy through UCP1-mediated mitochondrial uncoupling or by the activation of alternative UCP1-independent futile cycles.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

Brown adipose tissue metabolism in ob/ob mice: effects of a high-fat diet and adrenalectomy

1987 ◽  
Vol 253 (2) ◽  
pp. E149-E157
Author(s):  
H. K. Kim ◽  
D. R. Romsos
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Adipose Tissue Metabolism ◽  
High Carbohydrate ◽  
Bat Mitochondria ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Thermogenic Capacity

Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets partly by stimulating the low thermogenic capacity of their brown adipose tissue (BAT). Adrenalectomy, however, fails to prevent development of obesity in ob/ob mice fed a high-fat diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed a high-fat diet were thus examined. ob/ob mice fed the high-fat diet developed gross obesity despite normal BAT metabolism, as assessed by rates of norepinephrine turnover in BAT, GDP binding to BAT mitochondria, and GDP-inhibitable, chloride-induced mitochondrial swelling. Adrenalectomy failed to arrest the development of obesity or to influence BAT metabolism in ob/ob mice fed the high-fat diet. Development of obesity in ob/ob mice fed a high-fat diet is not associated with low thermogenic capacity of BAT or with adrenal secretions, as it is in ob/ob mice fed high-carbohydrate stock diets.

scholarly journals TM4SF5 Knockout Protects Mice from Diet-Induced Obesity Partly by Regulating Autophagy in Adipose Tissue

2021 ◽  
Author(s):  
Cheoljun Choi ◽  
Yeonho Son ◽  
Jinyoung Kim ◽  
Yoon Keun Cho ◽  
Abhirup Saha ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxidative Metabolism ◽  
Metabolic Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Regulatory Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Mtorc1 Signaling ◽  
Mitochondrial Oxidative Metabolism

Transmembrane 4 L six family member 5 (TM4SF5) functions as a sensor for lysosomal arginine levels and activates the mammalian target of rapamycin complex 1 (mTORC1). While the mTORC1 signaling pathway plays a key role in adipose tissue metabolism, the regulatory function of TM4SF5 in adipocytes remains unclear. This study aimed to establish a TM4SF5 knockout (KO) mouse model and investigated the effects of TM4SF5 KO on mTORC1 signaling-mediated autophagy and mitochondrial metabolism in adipose tissue. TM4SF5 expression was higher in inguinal white adipose tissue (iWAT) than in brown adipose tissue and significantly upregulated by a high-fat diet (HFD). TM4SF5 KO reduced mTORC1 activation and enhanced autophagy and lipolysis in adipocytes. RNA-seq analysis of TM4SF5 KO mouse iWAT showed that the expression of genes involved in peroxisome proliferator-activated receptor alpha signaling pathways and mitochondrial oxidative metabolism was upregulated. Consequently, TM4SF5 KO reduced adiposity and increased energy expenditure and mitochondrial oxidative metabolism. TM4SF5 KO prevented HFD-induced glucose intolerance and inflammation in adipose tissue. Collectively, our study demonstrated that TM4SF5 regulates autophagy and lipid catabolism in adipose tissue and suggested that TM4SF5 could be therapeutically targeted for the treatment of obesity-related metabolic diseases.

scholarly journals Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Danielle Yi ◽  
Hai P Nguyen ◽  
Jennie Dinh ◽  
Jose A Viscarra ◽  
Ying Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Target Genes ◽  
Critical Role ◽  
Direct Interaction ◽  
Fat Cell ◽  
Methyltransferase Activity ◽  
Promoter Regions ◽  
Brown Adipose ◽  
Thermogenic Capacity

Brown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1l, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the Ucp1 promoter and other BAT genes. Through a direct interaction, Dot1l is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1l is induced during brown fat cell differentiation and by cold exposure and that Dot1l and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1l ablation in mice using Ucp1-Cre prevents activation of Ucp1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1l plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

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