Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans

Genetically obese (ob/ob) mice develop insulin resistance in brown adipose tissue during the fifth week of life. Prior to this, at 26 days of age, oh/oh mice show a substantial increase in GDP binding to brownadipose-tissue mitochondria during acute cold exposure. When insulin resistance in brown fat develops, by 35 days of age, the increase in GDP binding in response to cold is markedly reduced. Studies with 2-deoxyglucose suggest that insulin resistance in brown adipose tissue could impair thermogenic responsiveness during acute cold exposure by limiting the ability of the tissue to take up glucose.

Download Full-text

Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity in rats measured by 18F-FDG PET

10.21203/rs.3.rs-20709/v2 ◽

2020 ◽

Author(s):

Bruno Halpern ◽

Marcio C Mancini ◽

Caroline Mendes ◽

Camila Maria Longo Machado ◽

Silvana Prando ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Mrna Expression ◽

Cold Exposure ◽

Fdg Pet ◽

Room Temperature ◽

Bat Activity ◽

Acute Cold Exposure ◽

Brown Adipose ◽

Thermogenic Capacity

Abstract Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. the gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression.Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.

Download Full-text

Relationship between cold-induced thermoregulation and spontaneous rapid body weight loss of aging F344 rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.5.r1115 ◽

1996 ◽

Vol 271 (5) ◽

pp. R1115-R1122 ◽

Cited By ~ 13

Author(s):

R. B. McDonald ◽

M. Florez-Duquet ◽

C. Murtagh-Mark ◽

B. A. Horwitz

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Physiological State ◽

Rapid Weight Loss ◽

Acute Cold Exposure ◽

Brown Adipose ◽

F344 Rats

We previously showed that, although cold-induced thermoregulation is attenuated in 26-mo-old male Fischer 344 (F344) rats, not all rats this age exhibit the same degree of cold-exposed hypothermia or diminished brown adipose tissue nonshivering thermogenic capacity. Examination of this heterogeneity suggested the hypothesis that it was associated with a difference in the physiological state between aged rats that were maintaining stable body weight versus those showing the rapid weight loss often occurring near the end of the rat's natural life span. To test this, we acutely exposed male F344 rats to cold (4 h at 6 degrees C) beginning at 24 mo of age. This exposure was weekly for the first 2 wk and then on alternate weeks as long as the rat's body weight was stable. If body weight progressively declined for 3-5 consecutive days, the rat's response to the acute cold exposure was again measured, as was that of two additional rats not displaying this rapid loss in body weight. If body temperature decreased during the cold exposure to intraperitoneal temperatures < or = 32.5 degrees C, the rat was killed with pentobarbital sodium and interscapular brown adipose tissue was removed. One of the age-matched controls was also killed at this time. The age at which body weight showed a spontaneous rapid decline ranged from 24.5 to 29 mos. All eight rats displaying spontaneous rapid weight loss had significant hypothermia during the acute cold exposure, whereas none of the eight weight-stable rats did. The development of hypothermia in the spontaneous rapid weight loss group was not, in general, observed before their weight loss. The weight loss and hypothermia were associated with lower levels of brown fat uncoupling protein and significant changes in body fat and protein. These data suggest that the development of senescence-related hypothermia occurs rapidly and is not a simple function of chronological age or the median life span of the animals. Furthermore, these data imply that the rate of aging in terms of maintenance of thermoregulatory homeostasis has both a gradual and rapid component, the latter being associated with a different physiological state than the former.

Download Full-text

Serotonin effect on deiodinating activity in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y03-068 ◽

2003 ◽

Vol 81 (7) ◽

pp. 747-751 ◽

Cited By ~ 2

Author(s):

Alessio Sullo ◽

Guglielmo Brizzi ◽

Nicola Maffulli

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Heat Production ◽

Cold Exposure ◽

Type Ii ◽

Indirect Measure ◽

Peripheral Tissues ◽

Brown Adipose ◽

The Brain

Serotonin (5-HT) and thyroid hormones are part of a complex system modulating eating behaviour and energy expenditure. 5'-Deiodinase (5'-D) converts the relatively inactive thyroxine (T4) to triiodothyronine (T3), and its activity is an indirect measure of T3 production in peripheral tissues, particularly in the brain, intrascapular brown adipose tissue (IBAT), heart, liver, and kidney. We evaluated the effect of 5-HT on 5'-D activity during basal conditions and after short (30 min) cold exposure (thyroid stimulating hormone stimulation test, TST). 5'-D activity was assessed in the liver, heart, brain, kidney, and IBAT. TST increases 5'-D activity in the brain, heart, and IBAT and decreases it in kidney, leaving it unchanged in the liver. 5-HT alone did not modify 5'-D activity in the organs under study but decreased it in the IBAT, heart, and brain when injected before the TST was administered. Our results confirm the important role of 5-HT in thermoregulation, given its peripheral site of action, in modulating heat production controlling intracellular T3 production. These effects are more evident when heat production is upregulated during cold exposure in organs containing type II 5'-D, such as the brain, heart, and IBAT, which are able to modify their function during conditions that alter energy balance. In conclusion, 5-HT may also act peripherally directly on the thyroid and organs containing type II 5'-D, thus controlling energy expenditure through heat production.Key words: serotonin, deiodinase activity, thyroid hormone, brown adipose tissue, thermogenesis, rat organs.

Download Full-text

The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa183 ◽

2020 ◽

Vol 105 (7) ◽

pp. 2203-2216 ◽

Cited By ~ 7

Author(s):

Oana C Kulterer ◽

Laura Niederstaetter ◽

Carsten T Herz ◽

Alexander R Haug ◽

Andrea Bileck ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Fdg Pet ◽

Brown Adipose ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Background Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg). Methods Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography ([18F]-FDG PET/CT). BAT function, CIEE, and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry, and high-resolution mass spectrometry, respectively. Results We found that active BAT is the major determinant of CIEE since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of an additional 20 kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory omega-3 fatty acids as well as cytochrome P450 products but decreased concentrations of some proinflammatory hydroxyeicosatetraenoic acids when compared with BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BAT-derived circulating factors (BATokines) DiHOME and 12-HEPE, only in BATpos individuals. Conclusions In summary, our data emphasize that BAT in humans is a major contributor toward cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool.

Download Full-text