Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans

Diet-induced thermogenesis (DIT) in young rats overeating a "cafeteria" (CAF) diet of palatable human foods is characterized by a chronic, propranolol-inhibitable elevation in resting metabolic rate [Formula: see text] and is associated with various changes in brown adipose tissue (BAT) that have been taken as evidence for BAT as the effector of DIT. But direct evidence for participation of BAT in DIT has been lacking. By employing a nonocclusive cannula to sample the venous effluent of interscapular BAT (IBAT) for analysis of its O2 content and measuring tissue blood flow with microspheres, we accomplished direct determination (Fick principle) of the O2 consumption of BAT in conscious CAF rats. In comparison with normophagic controls fed chow, the CAF rats exhibited a 43% increase in metabolizable energy intake, reduced food efficiency, a 22% elevation in resting [Formula: see text] at 28 °C (thermoneutrality) or 24 °C (housing temperature), and characteristic changes in the properties of their BAT (e.g., increased mass, protein content and mitochondrial GDP binding). They also exhibited the greater metabolic response to exogenous noradrenaline characteristic of CAF rats and the near elimination by propranolol of their elevation in [Formula: see text]. By the criterion of their elevated [Formula: see text], the CAF rats were exhibiting DIT at the time of the measurements of BAT blood flow and blood O2 levels. However, BAT O2 consumption was found to be no greater in the CAF rats than in the controls at either 28 or 24 °C. At 28 °C it accounted for less than 1% of whole body [Formula: see text]; at 24 °C it increased to about 10% of overall [Formula: see text] in both diet groups. Direct measurements of BAT O2 consumption during expression of the thermic response to a tube-fed meal were also made in conscious CAF and control rats. Both diet groups exhibited an approximately 15% increase in whole body [Formula: see text] at 90–120 min after the meal. The contribution by BAT to this increase was only 2–3% and did not differ significantly between groups. Thus, the results of these direct measurements of BAT O2 consumption in vivo do not support the theory that DIT in CAF rats is mainly due to increased BAT thermogenesis occurring either chronically or during assimilation of a meal. In further studies of the effector(s) of DIT in CAF rats, partial hepatectomy (two-thirds of the liver removed) was found to acutely reduce the resting [Formula: see text] of CAF rats by 1.85 mL/min, 2.3 times as much as in chow-fed controls. From this difference in response, it was estimated that in the CAF rats liver O2 consumption before hepatectomy exceeded that of the controls by about 1.5 mL/min, an amount that would be sufficient to fully account for the elevation in resting [Formula: see text] of the former. A major role for the liver in the DIT of CAF rats is thus suggested.Key words: cafeteria feeding, diet-induced thermogenesis, thermic effect of food, brown fat, liver.

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

Nature Communications ◽

10.1038/s41467-020-20665-4 ◽

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.

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Exercise and brain catecholamine relationships with brown adipose tissue and whole-body oxygen consumption in rats

Physiology & Behavior ◽

10.1016/0031-9384(88)90090-x ◽

1988 ◽

Vol 43 (1) ◽

pp. 9-12 ◽

Cited By ~ 5

Author(s):

John M. de Castro ◽

James O. Hill

Keyword(s):

Adipose Tissue ◽

Oxygen Consumption ◽

Brown Adipose Tissue ◽

Whole Body ◽

Brown Adipose

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Fatty acid synthesis in brown adipose tissue in relation to whole body synthesis in the cold-acclimated golden hamster (Mesocricetus auratus)

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(80)90179-4 ◽

1980 ◽

Vol 620 (1) ◽

pp. 10-17 ◽

Cited By ~ 22

Author(s):

Paul Trayhurn

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Fatty Acid Synthesis ◽

Golden Hamster ◽

Acid Synthesis ◽

Mesocricetus Auratus ◽

Whole Body ◽

Brown Adipose

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The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽

10.3390/cells10051122 ◽

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.

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KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

Journal of Endocrinology ◽

10.1530/joe-21-0016 ◽

2021 ◽

Author(s):

Mingsheng Ye ◽

Liping Luo ◽

Qi Guo ◽

Guanghua Lei ◽

Chao Zeng ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Notch Signaling ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Notch Signaling Pathway ◽

Whole Body ◽

Brown Adipocyte ◽

Metabolic Function ◽

Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

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CNS origins of the sympathetic nervous system outflow to brown adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.6.r1569 ◽

1999 ◽

Vol 276 (6) ◽

pp. R1569-R1578 ◽

Cited By ~ 70

Author(s):

Maryam Bamshad ◽

C. Kay Song ◽

Timothy J. Bartness

Keyword(s):

Nervous System ◽

Adipose Tissue ◽

Sympathetic Nervous System ◽

Brown Adipose Tissue ◽

Pseudorabies Virus ◽

Critical Role ◽

Hypothalamic Nucleus ◽

Brown Adipose ◽

Sympathetic Nervous ◽

Diet Induced Thermogenesis

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.

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Brown Adipose Tissue Activation by Cold Treatment Ameliorates Polycystic Ovary Syndrome in Rat

Frontiers in Endocrinology ◽

10.3389/fendo.2021.744628 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rongcai Ye ◽

Chunlong Yan ◽

Huiqiao Zhou ◽

Yuanyuan Huang ◽

Meng Dong ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Brown Adipose Tissue ◽

Therapeutic Strategy ◽

Polycystic Ovary ◽

Cold Treatment ◽

Whole Body ◽

Ovary Syndrome ◽

Bat Activity ◽

Brown Adipose

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

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