Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.

Increased heat generation from biological processes is inherent to homeothermy. Homeothermic species produce more heat from sustaining a more active metabolism as well as from reducing fuel efficie...

https://www.physiology.org/doi/pdf/10.1152/physrev.00009.2005

Thermogenic mechanisms and their hormonal regulation.

Adaptive nonshivering thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive nonshivering thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive nonshivering thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4C during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive nonshivering thermogenesis, however, no substitution of shivering by any adaptive nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive nonshivering thermogenesis has recurrently been implied, we did not find any indication of such thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive nonshivering thermogenesis in the cold.

Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold

There is a misbelief that the same animal has the same thermoneutral zone (TNZ) in different experimental setups. In reality, TNZ strongly depends on the physical environment and varies widely acro...

Selected Contribution: Ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality

The capacity for nonshivering thermogenesis (NST) was examined in 26- to 27-day cold-acclimated (CA) muscovy ducklings reared for 21 days at 4 degrees C. Metabolic rate and integrated electromyographic (EMG) muscle activity were measured at ambient temperature ranging from -10 to 28 degrees C. Compared with controls reared at 30 degrees C, CA ducklings were more resistant to cold and had higher peak metabolic rate in extreme cold. Shivering threshold temperature of CA ducklings was 14.2 degrees C lower than lower critical temperature, whereas for controls the two temperatures were similar. Thus CA ducklings exhibited an NST in moderate cold. In addition, at temperatures that produced shivering, EMG activity in CA duckling muscle was lesser than that of controls, even at a higher metabolic rate. Because these ducklings are devoid of brown adipose tissue, these results indicated an increased thermogenic efficiency of muscular activity in CA ducklings.

Potentiated muscular thermogenesis in cold-acclimated muscovy duckling

To explain tolerance of heat and cold in gerbils (Gerbillus campestris) in their natural environment, a comparative study was made of thermoregulatory reactions in these animals and white mice (Mus musculus) of the same body mass exposed for 2-3 h to ambient temperatures (Ta) ranging from -23 to 40 degrees C. Metabolic rate (MR), evaporative heat loss (EHL), colonic temperature (Tb), and electromyographic activity (EMG) were measured. Nonshivering thermogenesis (NST) was also evaluated from the increase in MR after norepinephrine injection. In gerbils, tolerance of cold was higher than in mice; there was no fall in Tb in cold-acclimated (CA) and control (TN) gerbils after 3 h of exposure at -20 and -10 degrees C Ta, respectively; peak MR (PMR) reached five to six times resting MR (RMR) in gerbils and four to five times in mice. In gerbils, RMR was 35% below that of mice. In TN gerbils, EHL did not increase before 38 degrees C Ta; EHL increased at 26 degrees C in mice. In both animals, cold acclimation increased cold tolerance, PMR, RMR, and NST. Low RMR, high Tb, and mainly burrowing habits preserve gerbils from overheating and save water in hot and arid environments, and a conspicuous tolerance of cold allows them to live and forage in the wild during the cold night.

Adaptation to extreme ambient temperatures in cold-acclimated gerbils and mice.

The site of the calorigenesis observed in birds after glucagon was sought in control and cold-acclimated (CA) ducklings. Twenty-four 6-wk-old muscovy ducklings were reared either at thermoneutrality (TN) (25 degrees C) or in the cold (4 degrees C) from the age of 1 wk. Glucagon-induced calorigenesis (GIC) was estimated at 25 degrees C after a peritoneal glucagon injection (103 nmol/kg). Glucagon induced a higher increase in animal heat production (indirect calorimetry) and body temperature in CA (+45% and +1.1 degrees C) than in control ducklings (+30% and +0.4 degree C). In CA ducklings, the perfusion rate (thermal clearance method) and temperature of gastrocnemius increased (+130% and +1.0 degree C) shortly after glucagon, whereas tissue oxygenation (polarography) decreased (-34%). There was no significant effect of glucagon in TN controls. These changes, which peaked 45-60 min after glucagon injection, indicated a prolonged increase of muscle O2 consumption in CA ducklings. Leg muscle blood flow (radioactive microspheres) measured 45 min after glucagon was slightly increased in controls (+20%; P < 0.05), while in CA ducklings, the increase was larger (+76%; P < 0.05). The arteriovenous difference in O2 content was not markedly affected by glucagon in both groups. These parameters indicated an increase in leg muscle O2 uptake in response to glucagon of +29% in controls and +76% in CA ducklings. In controls, 28% of the GIC measured in vivo could be attributed to whole body skeletal muscles, compared with 53% in CA ducklings. The remaining part might be accounted for mostly by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased role of skeletal muscle in the calorigenic response to glucagon of cold-acclimated ducklings.

To determine the effects of cold acclimation on the oxidative capacity of different tissues and their possible role in nonshivering thermogenesis (NST) in a desert rodent, the gerbil (Gerbillus campestris), measurements of cytochrome oxidase activity (COX) were performed on homogenates of liver, brown adipose tissue (BAT), and subsarcolemmal (SS) and intermyofibrillar (IMF) fractions of skeletal muscle. Total organ mass was also measured. Gerbils were maintained either at thermoneutrality (TN) or cold [4 degrees C, ambient temperature (Ta)] for 4 (CA4) or 8 (CA8) wk. A comparative study was made with mice (Mus musculus). Total and relative masses of BAT increased significantly in both gerbils and mice during cold acclimation, whereas muscle mass decreased in CA4 gerbils. Specific and total COX (TCOX) increased in the three tissues. A considerable increase (+170%, P less than 0.05) of TCOX and protein content in liver of CA4 gerbils compared with controls was observed, whereas no significant changes occurred in liver of CA4 mice. In muscle, an increase of TCOX in SS and a reduction in IMF cell compartments were noted. The increase in BAT oxidative capacity in CA4 gerbils represented only a small portion of that in liver (36%) and in SS fraction of muscle (41%) at the same stage of acclimation. The ability of the three tissues to contribute to components of thermogenesis in vivo was evaluated. The sum of oxidative capacity of the three tissues was largely above the peak metabolic rate (PMR), whereas that of muscle exceeded maximum shivering thermogenesis, which developed both in TN and CA4 gerbils.(ABSTRACT TRUNCATED AT 250 WORDS)

J. Chatonnet

Papers

Potentiated muscular thermogenesis in cold-acclimated muscovy duckling

Adaptation to extreme ambient temperatures in cold-acclimated gerbils and mice.

Increased role of skeletal muscle in the calorigenic response to glucagon of cold-acclimated ducklings.

Increase in cytochrome oxidase capacity of BAT and other tissues in cold-acclimated gerbils