scholarly journals Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon T. Bond ◽  
Emily J. King ◽  
Darren C. Henstridge ◽  
Adrian Tran ◽  
Sarah C. Moody ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Epigenetic Mechanisms ◽  
Adipocyte Size ◽  
Tripartite Motif ◽  
Specific Manner ◽  
Bona Fide ◽  
Developmental Role ◽  
Body Energy

AbstractThe effective storage of lipids in white adipose tissue (WAT) critically impacts whole body energy homeostasis. Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. However, in the current study we demonstrate that mice with deletion of Trim28 specifically in committed adipocytes, also develop obesity similar to global Trim28 deletion models, highlighting a post-developmental role for Trim28. These effects were exacerbated in female mice, contributing to the growing notion that Trim28 is a sex-specific regulator of obesity. Mechanistically, this phenotype involves alterations in lipolysis and triglyceride metabolism, explained in part by loss of Klf14 expression, a gene previously demonstrated to modulate adipocyte size and body composition in a sex-specific manner. Thus, these findings provide evidence that Trim28 is a bona fide, sex specific regulator of post-developmental adiposity and WAT function.

scholarly journals Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice

2019 ◽  
Vol 116 (47) ◽  
pp. 23822-23828 ◽  
Author(s):  
Shintaro Yamaguchi ◽  
Michael P. Franczyk ◽  
Maria Chondronikola ◽  
Nathan Qi ◽  
Subhadra C. Gunawardana ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Lipolytic Activity ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Adaptive Thermogenesis ◽  
Body Energy

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+–SIRT1–caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.

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

Abstract 327: Cardiac Regulation of Metabolic Homeostasis by Med13

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Chad E Grueter ◽  
Kedryn K Baskin ◽  
Christine M Kusminski ◽  
William Holland ◽  
Philipp E Scherer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transcriptional Activation ◽  
Energy Homeostasis ◽  
The Body ◽  
Whole Body ◽  
Mediator Complex ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Metabolite Production ◽  
Body Energy

Alterations in metabolism are a major component of cardiovascular disease associated with obesity and type 2 diabetes. The complex interplay between these three diseases poses a challenge for successful treatment and warrants further studies directed at understanding the intertissue communication between major metabolic organs. We previously identified a signaling pathway within the heart that modulates systemic energy homeostasis by regulation of Med13, a component of the kinase submodule of the Mediator Complex, in the heart. The Mediator Complex is a large, multiprotein complex that functions to integrate signal specific events with transcriptional activation and elongation in a context dependent manner. Our current work further delineates a mechanism by which Med13 in the heart functions to regulate whole body energy homeostasis. The increase in energy expenditure in Med13 transgenic (TG) mice is due in part to increased triglyceride uptake and beta-oxidation in white adipose tissue and liver. Additionally, the expression of Krebs Cycle and fatty acid oxidation genes are increased in adipose tissue and liver as measured by RNA seq and in metabolite production in Med13 Tg mice. Together, these results demonstrate the Mediator Complex regulates cardiac gene expression and metabolite production which communicates with energy depots within the body to modulate whole body energy homeostasis.

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 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.

Leptin is involved in the regulation of ovarian activity in fasted hens (Gallus domesticus)

2002 ◽  
Vol 2002 ◽  
pp. 3-3
Author(s):  
H. Paczoska-Eliasiewicz ◽  
M. Proszkowiec ◽  
A. Hrabia ◽  
A. Sechman ◽  
N. Raver ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasma Level ◽  
Energy Homeostasis ◽  
Gallus Domesticus ◽  
Whole Body ◽  
Ovarian Activity ◽  
Avian Reproduction ◽  
Reproductive Axis ◽  
Body Energy

In mammals leptin plays a key role in regulating the whole-body energy homeostasis and is important for for normal reproduction Much evidence indicates that leptin mediates the undernutrition-induced alterations of the reproductive axis (Ahima and Flier, 2000). In birds leptin gene was cloned in chickens (Taouis et al., 1998) and recombinant chicken leptin (chLep) was prepared in our laboratory (Raver et al., 1998). Unlike mammals, leptin is expressed not only in the adipose tissue but also in liver and leptin plasma level is lower in fasted than in fed hens (Dridi et al., 2000). However, the importance of leptin in avian reproduction is not known. Therefore, the aim of the present study was to examine whether in chickens leptin affects events occuring in the ovary during fasting.

Role of cell cycle regulators in adipose tissue and whole body energy homeostasis

2017 ◽  
Vol 75 (6) ◽  
pp. 975-987 ◽  
Author(s):  
I. C. Lopez-Mejia ◽  
J. Castillo-Armengol ◽  
S. Lagarrigue ◽  
L. Fajas
Keyword(s):  
Cell Cycle ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Cell Cycle Regulators ◽  
Body Energy

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.

Exercise and MEF2–HDAC interactions

2007 ◽  
Vol 32 (5) ◽  
pp. 852-856 ◽  
Author(s):  
Sean L. McGee
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Nuclear Export ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Positive Health ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
Body Energy ◽  
Skeletal Muscle Adaptations

Exercise increases the metabolic capacity of skeletal muscle, which improves whole-body energy homeostasis and contributes to the positive health benefits of exercise. This is, in part, mediated by increases in the expression of a number of metabolic enzymes, regulated largely at the level of transcription. At a molecular level, many of these genes are regulated by the class II histone deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5, through their interaction with myocyte enhancer factor 2 transcription factors. HDAC5 kinases, including 5′-AMP-activated protein kinase and protein kinase D, appear to regulate skeletal muscle metabolic gene transcription by inactivating HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate in exercise-induced gene expression and could be important for skeletal muscle adaptations to exercise.

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