Time-course microarrays reveal modulation of developmental, lipid metabolism and immune gene networks in intrascapular brown adipose tissue during the development of diet-induced obesity

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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Diet-induced Obesity and Brown Adipose Tissue

Obesity: Dietary Factors and Control ◽

10.1159/000420918 ◽

2015 ◽

pp. 81-95

Author(s):

Jean Himms-Hagen ◽

Jingying Cui

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Diet Induced Obesity ◽

Brown Adipose

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Does a high-fat diet-induced obesity model brown adipose tissue thermogenesis? A systematic review

Archives of Medical Science ◽

10.5114/aoms.2019.86781 ◽

2019 ◽

Author(s):

Gabriela S. Perez ◽

Gabriele D.S. Cordeiro ◽

Lucimeire S. Santos ◽

Djane D.A. Espírito-Santo ◽

Gilson T. Boaventura ◽

...

Keyword(s):

Systematic Review ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Selective loss of uncoupling protein mRNA in brown adipose tissue on deacclimation of cold-acclimated mice

Biochemistry and Cell Biology ◽

10.1139/o87-124 ◽

1987 ◽

Vol 65 (11) ◽

pp. 955-959 ◽

Cited By ~ 14

Author(s):

Hasmukh V. Patel ◽

Karl B. Freeman ◽

Michel Desautels

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cytochrome C Oxidase ◽

Time Course ◽

Uncoupling Protein ◽

Relative Proportion ◽

Cdna Probe ◽

Mitochondrial Content ◽

Brown Adipose ◽

Uncoupling Protein Mrna

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 °C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.

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Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Molecular Metabolism ◽

10.1016/j.molmet.2019.03.011 ◽

2019 ◽

Vol 24 ◽

pp. 1-17 ◽

Cited By ~ 8

Author(s):

Sabrina Gohlke ◽

Vyacheslav Zagoriy ◽

Alvaro Cuadros Inostroza ◽

Michaël Méret ◽

Carola Mancini ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Tissue Aging

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Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia

Biochemical Journal ◽

10.1042/bj2910109 ◽

1993 ◽

Vol 291 (1) ◽

pp. 109-113 ◽

Cited By ~ 23

Author(s):

R Burcelin ◽

J Kande ◽

D Ricquier ◽

J Girard

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Time Course ◽

Glucose Transporter ◽

Uncoupling Protein ◽

Mrna Level ◽

Diabetic Rats ◽

Plasma Insulin Concentration ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.

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Brown adipose tissue and lipid metabolism imaging

Methods ◽

10.1016/j.ymeth.2017.05.001 ◽

2017 ◽

Vol 130 ◽

pp. 105-113 ◽

Cited By ~ 14

Author(s):

Andreas Paulus ◽

Wouter van Marken Lichtenbelt ◽

Felix M. Mottaghy ◽

Matthias Bauwens

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Brown Adipose Tissue ◽

Brown Adipose

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The role of active brown adipose tissue (aBAT) in lipid metabolism in healthy Chinese adults

Lipids in Health and Disease ◽

10.1186/s12944-016-0310-8 ◽

2016 ◽

Vol 15 (1) ◽

Cited By ~ 5

Author(s):

Xiaoliang Shao ◽

Wei Yang ◽

Xiaonan Shao ◽

Chun Qiu ◽

Xiaosong Wang ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Brown Adipose Tissue ◽

Chinese Adults ◽

Brown Adipose ◽

Healthy Chinese

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Rapid changes in metabolic cold defense and GDP binding to brown adipose tissue mitochondria of rat pups

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.5.r1017 ◽

1993 ◽

Vol 264 (5) ◽

pp. R1017-R1023 ◽

Cited By ~ 1

Author(s):

G. Kortner ◽

K. Schildhauer ◽

O. Petrova ◽

I. Schmidt

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Time Course ◽

Developmental Changes ◽

Whole Body ◽

Rat Pups ◽

Brown Adipose ◽

Rapid Changes ◽

Whole Body Metabolism

To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled.

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