New approaches targeting brown adipose tissue transplantation as a therapy in obesity

Soler‐Vázquez, M. Carmen; Mera, Paula; Zagmutt, Sebastián; Serra, Dolors; Herrero, Laura

doi:10.1016/j.bcp.2018.07.022

Cited by 43 publications

(43 citation statements)

References 100 publications

(3 reference statements)

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“…The cycling frequency was kept at 60 rpm. The cycling intensity was increased so that at the end of the test, the subject reached~80% of the theoretical maximal heart rate and rating of perceived exertion no more than 17 (Borg scale [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Blood pressure and heart rate were monitored throughout the test.…”

Section: Exercise Intervention and Bicycle Ergometer Testmentioning

confidence: 99%

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: Exercise Intervention and Bicycle Ergometer Testmentioning

confidence: 99%

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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“…Conversely, increasing thermogenic activity, either by the transplantation of metabolically active BAT or by pharmacological treatment with beta-3 adrenoceptor agonists, alleviates the symptoms of type 2 diabetes [6,7]. Also, accumulating evidence suggests that the maintenance of BAT function is a viable strategy to circumvent obesity-mediated metabolic dysfunction [8,9].…”

Section: Introductionmentioning

confidence: 99%

Alpha-Linolenic Acid-Enriched Butter Promotes Fatty Acid Remodeling and Thermogenic Activation in the Brown Adipose Tissue

et al. 2020

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Supplementation with n-3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT). Agricultural products that are biofortified with α-linolenic acid (ALA), the precursor of n-3 LC PUFA, have been launched to the market, but their impact on BAT function is unknown. This study aimed to evaluate the effects of ALA-biofortified butter on lipid metabolism and thermogenic functions in the BAT. C57BL/6 mice were fed a high-fat diet containing ALA-biofortified butter (n3Bu, 45% calorie from fat) for ten weeks in comparison with the isocaloric high-fat diets prepared from conventional butter or margarine. The intake of n3Bu significantly reduced the whitening of BAT and increased the thermogenesis in response to acute-cold treatment. Also, n3Bu supplementation is linked with the remodeling of BAT by promoting bioconversion into n-3 LC PUFA, FA elongation and desaturation, and mitochondrial biogenesis. Taken together, our results support that ALA-biofortified butter is a novel source of n-3 PUFA, which potentiates the BAT thermogenic function.

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“…As an energy-consuming, endocrine organ, BAT promotes weight loss and metabolic fitness when activated or transplanted in rodents (Soler-Vazquez et al, 2018). In humans, the activity of BAT has been repeatedly reported to be inversely associated with body mass index (Betz and Enerback, 2011;Tam et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue

Huang

Zhang

Heck

et al. 2020

Preprint

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In humans, brown adipose tissue (BAT) undergoes progressive involution or atrophy with increasing age, as manifested by decreased prevalence and mass, transformation to white adipose tissue (WAT), and reduction in thermogenic activity. This involution process cannot be fully recapitulated in rodent models and thus underlying cellular mechanisms are poorly understood. Here, we show that the interscapular BAT (iBAT) in rabbits involutes rapidly in early life, similarly to that in humans. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied with the loss of brown adipogenic competence of their precursor cells. Through single-cell RNA sequencing, we surveyed the heterogenous populations of mesenchymal cells within the stromal vascular fraction of rabbit and human iBAT. An analogous FSTL1 high population of brown adipocyte progenitors exists in both species while gradually disappear during iBAT involution in rabbits. In mice, FSTL1 is highly expressed by adipocyte progenitors in iBAT and genetic deletion of FSTL1 causes defective WNT signaling and iBAT atrophy in neonates. Our results underscore the BAT-intrinsic contribution from FSTL1 high progenitors to age-related tissue involution and point to a potential therapeutic approach for obesity and its comorbidities. HIGHLIGHTS• Rabbit BAT irreversibly transforms to WAT before puberty.• iBAT adipocyte progenitors reprogram transcriptome and lose brown adipogenic ability.• Comparable FSTL1 high brown adipocyte progenitors exist in rabbit and human iBAT.• Loss of FSTL1 in brown adipocyte progenitors causes iBAT atrophy in mice.

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New approaches targeting brown adipose tissue transplantation as a therapy in obesity

Cited by 43 publications

References 100 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

Alpha-Linolenic Acid-Enriched Butter Promotes Fatty Acid Remodeling and Thermogenic Activation in the Brown Adipose Tissue

Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue

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