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.

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 Essential role of systemic iron mobilization and redistribution for adaptive thermogenesis through HIF2-α/hepcidin axis

2021 ◽  
Vol 118 (40) ◽  
pp. e2109186118
Author(s):  
Jin-Seon Yook ◽  
Mikyoung You ◽  
Jiyoung Kim ◽  
Ashley M. Toney ◽  
Rong Fan ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Hypoxia Inducible Factor ◽  
Whole Body ◽  
Iron Mobilization ◽  
Adaptive Thermogenesis ◽  
Beige Fat ◽  
Biogenesis Of Mitochondria ◽  
Body Energy

Iron is an essential biometal, but is toxic if it exists in excess. Therefore, iron content is tightly regulated at cellular and systemic levels to meet metabolic demands but to avoid toxicity. We have recently reported that adaptive thermogenesis, a critical metabolic pathway to maintain whole-body energy homeostasis, is an iron-demanding process for rapid biogenesis of mitochondria. However, little information is available on iron mobilization from storage sites to thermogenic fat. This study aimed to determine the iron-regulatory network that underlies beige adipogenesis. We hypothesized that thermogenic stimulus initiates the signaling interplay between adipocyte iron demands and systemic iron liberation, resulting in iron redistribution into beige fat. To test this hypothesis, we induced reversible activation of beige adipogenesis in C57BL/6 mice by administering a β3-adrenoreceptor agonist CL 316,243 (CL). Our results revealed that CL stimulation induced the iron-regulatory protein–mediated iron import into adipocytes, suppressed hepcidin transcription, and mobilized iron from the spleen. Mechanistically, CL stimulation induced an acute activation of hypoxia-inducible factor 2-α (HIF2-α), erythropoietin production, and splenic erythroid maturation, leading to hepcidin suppression. Disruption of systemic iron homeostasis by pharmacological HIF2-α inhibitor PT2385 or exogenous administration of hepcidin-25 significantly impaired beige fat development. Our findings suggest that securing iron availability via coordinated interplay between renal hypoxia and hepcidin down-regulation is a fundamental mechanism to activate adaptive thermogenesis. It also provides an insight into the effects of adaptive thermogenesis on systemic iron mobilization and redistribution.

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.

scholarly journals Brown adipose tissue transplantation improves whole-body energy metabolism

Cell Research ◽  
2013 ◽  
Vol 23 (6) ◽  
pp. 851-854 ◽  
Author(s):  
Xiaomeng Liu ◽  
Zongji Zheng ◽  
Xiaoming Zhu ◽  
Minghui Meng ◽  
Lan Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Brown Adipose Tissue ◽  
Tissue Transplantation ◽  
Whole Body ◽  
Brown Adipose ◽  
Body Energy

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

2017 ◽  
Vol 61 (11) ◽  
pp. 1700261 ◽  
Author(s):  
Yilin You ◽  
Xiaoxue Yuan ◽  
Xiaomeng Liu ◽  
Chen Liang ◽  
Minghui Meng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Brown Adipose Tissue ◽  
Mitochondrial Function ◽  
Whole Body ◽  
Brown Adipose ◽  
Body Energy

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.

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 Disruption of Peripheral Leptin Signaling in Mice Results in Hyperleptinemia without Associated Metabolic Abnormalities

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3987-3997 ◽  
Author(s):  
Kaiying Guo ◽  
Julie E. McMinn ◽  
Thomas Ludwig ◽  
Yi-Hao Yu ◽  
Guoqing Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Food Intake ◽  
Leptin Receptor ◽  
Feedback Regulation ◽  
Whole Body ◽  
Negative Feedback Regulation ◽  
Leptin Signaling ◽  
Relative Contribution ◽  
Body Energy

Although central leptin signaling appears to play a major role in the regulation of food intake and energy metabolism, the physiological role of peripheral leptin signaling and its relative contribution to whole-body energy metabolism remain unclear. To address this question, we created a mouse model (Cre-Tam mice) with an intact leptin receptor in the brain but a near-complete deletion of the signaling domain of leptin receptor in liver, adipose tissue, and small intestine using a tamoxifen (Tam)-inducible Cre-LoxP system. Cre-Tam mice developed marked hyperleptinemia (∼4-fold; P < 0.01) associated with 2.3-fold increase (P < 0.05) in posttranscriptional production of leptin. Whereas this is consistent with the disruption of a negative feedback regulation of leptin production in adipose tissue, there were no discernable changes in energy balance, thermoregulation, and insulin sensitivity. Hypothalamic levels of phosphorylated signal transducer and activator of transcription 3, neuropeptide expression, and food intake were not changed despite hyperleptinemia. The percentage of plasma-bound leptin was markedly increased (90.1–96 vs. 41.8–74.7%; P < 0.05), but plasma-free leptin concentrations remained unaltered in Cre-Tam mice. We conclude from these results that 1) the relative contribution to whole-body energy metabolism from peripheral leptin signaling is insignificant in vivo, 2) leptin signaling in adipocyte constitutes a distinct short-loop negative feedback regulation of leptin production that is independent of tissue metabolic status, and 3) perturbation of peripheral leptin signaling alone, although increasing leptin production, may not be sufficient to alter the effective plasma levels of leptin because of the counter-regulatory increase in the level of leptin binding protein(s).

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