Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus

Rodovalho, S.; Rachid, Briana; de-Lima-Júnior, José C.; Sande‐Lee, Simone van de; Morari, Joseane; Carvalho, Humberto M.; Amorim, Bárbara Juarez; Tincani, Álfio José; Chaim, Élinton Adami; Pareja, José Carlos; Saad, Mário J.A.; Folli, Franco; Ramos, Celso Darío; Geloneze, Bruno; Velloso, Lı́cio A.

doi:10.1038/ijo.2017.152

Cited by 15 publications

(15 citation statements)

References 57 publications

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“…Interestingly, in the same study, there was no association between 12.5% weight loss and cold‐induced BAT GU even though subjects with obesity had high BAT GU values . In contrast to another study in subjects with morbid obesity, after 8 months of surgery, body mass reduction of around 28% had a more efficient effect to induce BAT activation in non‐diabetic than in subjects with diabetes . Surprisingly, in the present study, there was a significant reduction in BAT mass without any changes in body weight or cold‐induced BAT GU rate.…”

Section: Discussioncontrasting

confidence: 78%

Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity

Motiani

Teuho

Saari

et al. 2019

Obesity Science & Practice

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Summary Introduction New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold‐stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. Methods Healthy sedentary men ( n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m −2 ; VO 2 max 39 [7.6] mL min −1 kg −1 ) participated in a 6‐week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [ 18 F]fluorodeoxyglucose positron emission tomography–magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico‐thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. Results Cold exposure increased supraclavicular BAT GU by threefold ( p < 0.001), energy expenditure by 59% ( p < 0.001) and plasma fatty acids ( p < 0.01). Exercise training had no effect on cold‐induced GU in BAT or neck muscles. Training increased aerobic capacity ( p = 0.01) and decreased visceral fat ( p = 0.02) and cervico‐thoracic BAT mass ( p = 0.003). Additionally, training decreased very low‐density lipoprotein particle size ( p = 0.04), triglycerides within chylomicrons ( p = 0.04) and small high‐density lipoprotein ( p = 0.04). Conclusions Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.

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Section: Discussioncontrasting

confidence: 78%

Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity

Motiani

Teuho

Saari

et al. 2019

Obesity Science & Practice

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“…Employing [18F]-fluorodeoxyglucose (FDG) uptake as determined by positron emission tomography combined with X-ray computed tomography (FDG-PET/CT), studies have identified a number of factors that are physiologically related to increased BAT activity, such as cold-exposure, leanness, youth, physical activity and the female gender [13,67,72]. Conversely, in pathological conditions such as obesity and T2D not only is baseline BAT glucose uptake low, but the capacity of inducing its activity by different approaches is impaired [48,54].…”

Section: Introductionmentioning

confidence: 99%

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

et al. 2019

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BackgroundInflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue.MethodsThe relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice.FindingsIL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression.InterpretationIL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function.FundSao Paulo Research Foundation grant 2013/07607-8.

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“…Additionally, BS displayed a beneficial impact on the metabolic activity of BAT in morbidly obese patients 2 . The increase in brown/beige adipose tissue activity related to surgery-induced weight loss occurs independently of changes in hypothalamic activity 20 and BAT activity was found to be increased in obese nondiabetic and unchanged in obese diabetic subjects submitted to bariatric operation 21 . increased BAT thermogenesis, mediated by higher levels of growth hormone and insulin growth factor 1 6 .…”

Section: Discussionmentioning

confidence: 88%

“…. However, there are few studies showing the effects of BS on BAT and these reports present contrasting data regarding the surgery’s benefits 2 , 10 , 20 , 21 , 27 . Obese subjects showed increased non-shivering thermogenesis in BAT one year after surgery-induced weight loss, demonstrating that BAT can be recruited after bariatric procedures in humans 27 .…”

Section: Discussionmentioning

confidence: 99%

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Duodenal-Jejunal Bypass Reduces Lipid Accumulation in the Brown Adipose Tissue of Hypothalamic Obese Rats

Ceglarek

Guareschi

Moreira-Soares

et al. 2020

ABCD, arq. bras. cir. dig.

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Background: Thermogenic activity in the brown adipose tissue (BAT) of obese individuals is reduced, and this condition may be modified by bariatric surgery (BS). Aim: To characterize fat deposition in BAT from hypothalamic obese (HyO) rats submitted to duodenal-jejunal-bypass (DJB) surgery. Methods: For induction of hypothalamic obesity, newborn male Wistar rats were treated with subcutaneous injections of monosodium glutamate (MSG). The control (CTL) group received saline solution. At 90 days, the HyO rats were submitted to DJB or sham operation, generating the HyO-DJB and HyO-SHAM groups. At 270 days, the rats were euthanized, and the BAT was weighed and submitted to histological analysis. Results: Compared to BAT from CTL animals, the BAT from HyO-SHAM rats displayed increased weight, hypertrophy with greater lipid accumulation and a reduction in nucleus number. DJB effectively increased nucleus number and normalized lipid deposition in the BAT of HyO-SHAM rats, similar to that observed in CTL animals. Conclusion: DJB surgery avoided excessive lipid deposition in the BAT of hypothalamic obese rats, suggesting that this procedure could reactivate thermogenesis in BAT, and contribute to increase energy expenditure.

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Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus

Abstract: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.

Cited by 15 publications

References 57 publications

Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity

Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

Duodenal-Jejunal Bypass Reduces Lipid Accumulation in the Brown Adipose Tissue of Hypothalamic Obese Rats

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