scholarly journals Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

2020 ◽  
Vol 375 (1793) ◽  
pp. 20190135 ◽  
Author(s):  
Naresh C. Bal ◽  
Muthu Periasamy
Keyword(s):  
Energy Homeostasis ◽  
Atp Hydrolysis ◽  
Calcium Atpase ◽  
Whole Body ◽  
Signalling Molecule ◽  
Brown Adipose ◽  
Pump Activity ◽  
Body Energy ◽  
Shivering Thermogenesis

Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca 2+ -cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca 2+ transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

scholarly journals The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Jamie I. van der van der Vaart ◽  
Mariëtte R. Boon ◽  
Riekelt H. Houtkooper
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Ampk Signaling ◽  
Mitochondrial Homeostasis ◽  
Brown Adipose ◽  
Metabolic Stresses ◽  
Amp Activated Protein Kinase ◽  
Body Energy

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

2006-P: The Role of Adipose Tissue-Resident Eosinophils in Adipocyte Metabolism and Whole-Body Energy Homeostasis

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2006-P ◽  
Author(s):  
TING LI ◽  
WILLIAM LESUER ◽  
ABHILASHA SINGH ◽  
JAMES D. HERNANDEZ ◽  
XIAODONG ZHANG ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Body Energy

scholarly journals The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction

2016 ◽  
Vol 397 (8) ◽  
pp. 709-724 ◽  
Author(s):  
José Pedro Castro ◽  
Tilman Grune ◽  
Bodo Speckmann
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Reactive Oxygen ◽  
Whole Body ◽  
Oxygen Species ◽  
Body Energy

Abstract White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.

Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning

2020 ◽  
Vol 40 (1) ◽  
pp. 25-49 ◽  
Author(s):  
Nishan Sudheera Kalupahana ◽  
Bimba Lakmini Goonapienuwala ◽  
Naima Moustaid-Moussa
Keyword(s):  
Fatty Acids ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Omega 3 ◽  
Brown Adipose ◽  
Body Energy

White adipose tissue (WAT) and brown adipose tissue (BAT) are involved in whole-body energy homeostasis and metabolic regulation. Changes to mass and function of these tissues impact glucose homeostasis and whole-body energy balance during development of obesity, weight loss, and subsequent weight regain. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which have known hypotriglyceridemic and cardioprotective effects, can also impact WAT and BAT function. In rodent models, these fatty acids alleviate obesity-associated WAT inflammation, improve energy metabolism, and increase thermogenic markers in BAT. Emerging evidence suggests that ω-3 PUFAs can also modulate gut microbiota impacting WAT function and adiposity. This review discusses molecular mechanisms, implications of these findings, translation to humans, and future work, especially with reference to the potential of these fatty acids in weight loss maintenance.

scholarly journals Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1693 ◽  
Author(s):  
Daniel J. Torres ◽  
Matthew W. Pitts ◽  
Ann C. Hashimoto ◽  
Marla J. Berry
Keyword(s):  
Knockout Mice ◽  
Energy Homeostasis ◽  
Leptin Resistance ◽  
Whole Body ◽  
Metabolism Regulation ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Brown Adipose ◽  
Whole Body Metabolism

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.

scholarly journals SIRT2 Suppresses Adipocyte Differentiation by Deacetylating FOXO1 and Enhancing FOXO1's Repressive Interaction with PPARγ

2009 ◽  
Vol 20 (3) ◽  
pp. 801-808 ◽  
Author(s):  
Fei Wang ◽  
Qiang Tong
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Adipocyte Differentiation ◽  
Critical Role ◽  
Whole Body ◽  
Nutrient Deprivation ◽  
Metabolic Functions ◽  
Brown Adipose ◽  
Body Energy

Sirtuin family of proteins possesses NAD-dependent deacetylase and ADP ribosyltransferase activities. They are found to respond to nutrient deprivation and profoundly regulate metabolic functions. We have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue. Because adipose tissue is a key metabolic organ playing a critical role in whole body energy homeostasis, we went on to explore the function of SIRT2 in adipose tissue. We found short-term food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues. Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in white adipose tissue. Intraperitoneal injection of a β-adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue. Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis. SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-glucose (1 g/l) or low-insulin (100 nM) condition. Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to promote FOXO1's binding to PPARγ and subsequent repression on PPARγ transcriptional activity. Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation.

scholarly journals Identification and characterization of distinct murine brown adipocyte lineages

2020 ◽  
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Body Energy

AbstractBrown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. While increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Using single cell RNA sequencing of the stromal vascular fraction of murine BAT and analysis of 67 brown preadipocyte and adipocyte clones we unravel heterogeneity within brown preadipocytes. Statistical analysis of gene expression profiles from these clones identifies markers distinguishing brown adipocyte lineages. We confirm the presence of distinct brown adipocyte populations in vivo using three identified markers; Eif5, Tcf25, and Bin1. Functionally, we demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that Bin1 marks a dormant brown adipocyte type. The existence of multiple brown adipocyte lineages suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct function in thermogenesis and the regulation of whole body energy homeostasis.

scholarly journals Allicin regulates energy homeostasis through brown adipose tissue

2019 ◽  
Author(s):  
Chuanhai Zhang ◽  
Xiaoyun He ◽  
Yao Sheng ◽  
Jia Xu ◽  
Cui Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Promising Therapeutic Approach ◽  
Treatment Of Obesity

AbstractBackground/objectives:Disorder of energy homeostasis can lead to a variety of metabolic diseases, especially obesity. Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a main bioactive ingredient in garlic, has multiple biology and pharmacological function. However, the role of Allicin, in the regulation of metabolic organ, especially the role of activation of BAT, has not been well studied. Here, we analyzed the role of Allicin in whole-body metabolism and the activation of BAT.Results:Allicin had a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in diet-introduced obesity (DIO) mice. Then we find that Allicin can strongly activate brown adipose tissue (BAT). The activation of brown adipocyte treated with Allicin was also confirmed in mouse primary brown adipocytes.Conclusion:Allicin can ameliorate obesity through activating brown adipose tissue. Our findings provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

scholarly journals Orexin modulates brown adipose tissue thermogenesis

2012 ◽  
Vol 3 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Christopher J. Madden ◽  
Domenico Tupone ◽  
Shaun F. Morrison
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Pathological Conditions ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
The Central Nervous System ◽  
Conceptual Overview ◽  
Shivering Thermogenesis

AbstractNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulation. In addition, activations of BAT have important implications for energy homeostasis due to the metabolic consumption of energy reserves entailed in the production of heat in this tissue. In this conceptual overview, we describe the role of orexins/hypocretins within the central nervous system in the modulation of thermogenesis in BAT under several physiological conditions. Within this framework, we consider potential neural mechanisms underlying the pathological conditions associated with the absence of the central orexinergic modulation of BAT thermogenesis and energy expenditure. Overall, the experimental basis for our understanding of the role of central orexin in regulating body temperature and energy homeostasis provides an illustrative example that highlights several general principles and caveats that should help guide future investigations of the neurochemical regulation of thermogenesis and metabolism.

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