Brown adipose tissue: a potential target in the fight against obesity and the metabolic syndrome

2015 ◽  
Vol 129 (11) ◽  
pp. 933-949 ◽  
Author(s):  
Laurence Poekes ◽  
Nicolas Lanthier ◽  
Isabelle A. Leclercq

BAT (brown adipose tissue) is the main site of thermogenesis in mammals. It is essential to ensure thermoregulation in newborns. It is also found in (some) adult humans. Its capacity to oxidize fatty acids and glucose without ATP production contributes to energy expenditure and glucose homoeostasis. Brown fat activation has thus emerged as an attractive therapeutic target for the treatment of obesity and the metabolic syndrome. In the present review, we integrate the recent advances on the metabolic role of BAT and its relation with other tissues as well as its potential contribution to fighting obesity and the metabolic syndrome.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Cornelia Brendle ◽  
Norbert Stefan ◽  
Eva Grams ◽  
Martin Soekler ◽  
Christian la Fougère ◽  
...  

AbstractThe determinants of brown adipose tissue (BAT) activity are not yet known in detail but might serve as future therapeutic targets against obesity and the metabolic syndrome. We analyzed 235 datasets of lymphoma patients with two PET/CT examinations at different time points retrospectively. We assessed the anthropometric characteristics, features related to the metabolic syndrome, thyroid dysfunction, season of the PET/CT examination, weight change, prior cancer history, lymphoma subgroups, disease activity, and specific lymphoma-related therapies, and evaluated their association with BAT activity. We found BAT activity in 12% of all examinations, and the incidence of BAT activity after initially negative examinations was 10%. In multivariate regression analysis, the prevalence of BAT activity was associated with age, body mass index, sex, the season of the examination, diabetes mellitus, arterial hypertension, and medication on the beta-receptors. New BAT activity arose more often in patients without preceding lymphoma-related therapy. No specific medication was associated with BAT activity. In conclusion, this study confirms the potential connection of BAT with the metabolic syndrome. Preceding lymphoma-related therapy might have an inhibitory effect on the recruitment of BAT.


Theranostics ◽  
2020 ◽  
Vol 10 (18) ◽  
pp. 8197-8210 ◽  
Author(s):  
Xueying Zhou ◽  
Zhelong Li ◽  
Meihao Qi ◽  
Ping Zhao ◽  
Yunyou Duan ◽  
...  

2014 ◽  
Vol 170 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Zhaoyun Zhang ◽  
Aaron M Cypess ◽  
Qing Miao ◽  
Hongying Ye ◽  
Chong Wee Liew ◽  
...  

ObjectivePrevious studies have shown that active brown adipose tissue (BAT) is present in adults and may play important roles in the regulation of energy homeostasis. However, nearly every study has been carried out in patients undergoing scanning for cancer surveillance (CS), whose metabolism and BAT activity may not reflect those of healthy individuals. The objective of this study was to investigate the prevalence and predictors of active BAT in Chinese adults, particularly in healthy individuals.DesignA total of 31 088 consecutive subjects aged ≥18 years who had undergone positron emission tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this study.MethodsWe measured BAT activity via18F-fluorodeoxyglucose PET/CT in subjects who had undergone scanning for either a routine medical checkup (MC) or CS in Shanghai. Then, we investigated the predictors of active BAT, particularly in healthy individuals.ResultsIn both groups, the prevalence of BAT was higher in women than in men. Using a multivariate logistic analysis, we found age, sex, BMI, and high thyroid glucose uptake to be significant predictors of BAT activity in the MC group. Similarly, we found age, sex, and BMI to be significant predictors of BAT activity, but not thyroid high glucose uptake, in the CS group.ConclusionsIn Chinese adults, BAT activity inversely correlates with BMI and thyroid high glucose uptake, which reinforces the central role of brown fat in adult metabolism and provides clues to a potential means for treating the metabolic syndrome.


Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1482
Author(s):  
Ahmad Agil ◽  
Miguel Navarro-Alarcon ◽  
Fatma Abo Zakaib Ali ◽  
Ashraf Albrakati ◽  
Diego Salagre ◽  
...  

Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted.


2006 ◽  
Vol 27 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Helen J. Atherton ◽  
Nigel J. Bailey ◽  
Wen Zhang ◽  
John Taylor ◽  
Hilary Major ◽  
...  

The mobilization of triacylglycerides from storage in adipocytes to the liver is a vital response to the fasting state in mammalian metabolism. This is accompanied by a rapid translational activation of genes encoding mitochondrial, microsomal, and peroxisomal β-oxidation in the liver, in part under the regulation of peroxisome proliferator-activated receptor-α (PPAR-α). A failure to express PPAR-α results in profound metabolic perturbations in muscle tissue as well as the liver. These changes represent a number of deficits that accompany diabetes, dyslipidemia, and the metabolic syndrome. In this study, the metabolic role of PPAR-α has been investigated in heart, skeletal muscle, liver, and adipose tissue of PPAR-α null mice at 1 mo of age using metabolomics. To maximize the coverage of the metabolome in these tissues, 1H-NMR spectroscopy, magic angle spinning 1H-NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry were used to examine metabolites in aqueous tissue extracts and intact tissue. The data were analyzed by the multivariate approaches of principal components analysis and partial least squares. Across all tissues, there was a profound decrease in glucose and a number of amino acids, including glutamine and alanine, and an increase in lactate, demonstrating that a failure to express PPAR-α results in perturbations in glycolysis, the citric acid cycle, and gluconeogenesis. Furthermore, despite PPAR-α being weakly expressed in adipose tissue, a profound metabolic perturbation was detected in this tissue.


2017 ◽  
Vol 12 (2) ◽  
pp. 130-138 ◽  
Author(s):  
Meng Dong ◽  
Jun Lin ◽  
Wonchung Lim ◽  
Wanzhu Jin ◽  
Hyuek Jong Lee

2020 ◽  
Vol 375 (1793) ◽  
pp. 20190134 ◽  
Author(s):  
Martin Jastroch ◽  
Frank Seebacher

Endothermy changes the relationship between organisms and their environment fundamentally, and it is therefore of major ecological and evolutionary significance. Endothermy is characterized by non-shivering thermogenesis, that is metabolic heat production in the absence of muscular activity. In many eutherian mammals, brown adipose tissue (BAT) is an evolutionary innovation that facilitates non-shivering heat production in mitochondria by uncoupling food-derived substrate oxidation from chemical energy (ATP) production. Consequently, energy turnover is accelerated resulting in increased heat release. The defining characteristics of BAT are high contents of mitochondria and vascularization, and the presence of uncoupling protein 1. Recent insights, however, reveal that a range of stimuli such as exercise, diet and the immune system can cause the browning of white adipocytes, thereby increasing energy expenditure and heat production even in the absence of BAT. Here, we review the molecular mechanisms that cause browning of white adipose tissue, and their potential contribution to thermoregulation. The significance for palaeophysiology lies in the presence of adipose tissue and the mechanisms that cause its browning and uncoupling in all amniotes. Hence, adipocytes may have played a role in the evolution of endothermy beyond the more specific evolution of BAT in eutherians. This article is part of the theme issue ‘Vertebrate palaeophysiology’.


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Umesh D. Wankhade ◽  
Michael Shen ◽  
Hariom Yadav ◽  
Keshari M. Thakali

Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and “beige” adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed.


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