Sympathetic Outflow to Brown Adipose Tissue and Metabolic Heat Production in Adult, Aged, and Cold-Acclimated Adult Mice

Heat production in brown adipose tissue contributes to cold defense, to stress-induced increases in body temperature, and to energy balance. Elucidating the functional organization of the central network controlling the sympathetic outflow to brown adipose tissue could provide a framework for understanding how dysregulation of thermogenesis contributes to hyperthermia and to obesity.

Download Full-text

Cold-Induced Thermoregulation and Biological Aging

Physiological Reviews ◽

10.1152/physrev.1998.78.2.339 ◽

1998 ◽

Vol 78 (2) ◽

pp. 339-358 ◽

Cited By ~ 77

Author(s):

MARIA FLOREZ-DUQUET ◽

ROGER B. McDONALD

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Heat Production ◽

Biological Aging ◽

Metabolic Heat ◽

Age Related ◽

Brown Adipose ◽

Shivering Thermogenesis ◽

Thermogenic Capacity

Florez-Duquet, Maria, and Roger B. McDonald. Cold-Induced Thermoregulation and Biological Aging. Physiol. Rev. 78: 339–358, 1998. — Aging is associated with diminished cold-induced thermoregulation (CIT). The mechanisms accounting for this phenomenon have yet to be clearly elucidated but most likely reflect a combination of increased heat loss and decreased metabolic heat production. The inability of the aged subject to reduce heat loss during cold exposure is associated with diminished reactive tone of the cutaneous vasculature and, to a lesser degree, alterations in the insulative properties of body fat. Cold-induced metabolic heat production via skeletal muscle shivering thermogenesis and brown adipose tissue nonshivering thermogenesis appears to decline with age. Few investigations have directly linked diminished skeletal muscle shivering thermogenesis with the age-related reduction in cold-induced thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass and metabolic activity are cited as evidence for decreased heat production via shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling protein (UCP) levels are cited as evidence for attenuated brown adipose tissue cold-induced nonshivering thermogenic capacity during aging. The age-related reduction in brown fat nonshivering thermogenic capacity most likely reflects altered cellular signal transduction rather than changes in neural and hormonal signaling. The discussion in this review focuses on how alterations in CIT during the life span may offer insight into possible mechanisms of biological aging. Although the preponderance of evidence presented here demonstrates that CIT declines with chronological time, the mechanism reflecting this attenuated function remains to be elucidated. The inability to draw definitive conclusions regarding biological aging and CIT reflects the lack of a clear definition of aging. It is unlikely that the mechanisms accounting for the decline in cold-induced thermoregulation during aging will be determined until biological aging is more precisely defined.

Download Full-text

Plasticity of non-shivering thermogenesis and brown adipose tissue in high-altitude deer mice

Journal of Experimental Biology ◽

10.1242/jeb.242279 ◽

2021 ◽

Author(s):

Soren Z. Coulson ◽

Cayleih E. Robertson ◽

Sajeni Mahalingam ◽

Grant B. McClelland

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Altitude ◽

Heat Production ◽

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Deer Mice ◽

Brown Adipose ◽

Hypoxia Acclimation ◽

Shivering Thermogenesis

High altitude environments challenge small mammals with persistent low ambient temperatures that require high rates of aerobic heat production in face of low O2 availability. An important component of thermogenic capacity in rodents is non-shivering thermogenesis (NST) mediated by uncoupled mitochondrial respiration in brown adipose tissue (BAT). NST is plastic, and capacity for heat production increases with cold acclimation. However, in lowland native rodents, hypoxia inhibits NST in BAT. We hypothesize that highland deer mice (Peromyscus maniculatus) overcome the hypoxic inhibition of NST through changes in BAT mitochondrial function. We tested this hypothesis using lab born and raised highland and lowland deer mice, and a lowland congeneric (P. leucopus), acclimated to either warm normoxia (25°C, 760 mmHg) or cold hypoxia (5°C, 430 mmHg). We determined the effects of acclimation and ancestry on whole-animal rates of NST, the mass of interscapular BAT (iBAT), and uncoupling protein (UCP)-1 protein expression. To identify changes in mitochondrial function, we conducted high-resolution respirometry on isolated iBAT mitochondria using substrates and inhibitors targeted to UCP-1. We found that rates of NST increased with cold hypoxia acclimation but only in highland deer mice. There was no effect of cold hypoxia acclimation on iBAT mass in any group, but highland deer mice showed increases in UCP-1 expression and UCP-1 stimulated mitochondrial respiration in response to these stressors. Our results suggest that highland deer mice have evolved to increase the capacity for NST in response to chronic cold hypoxia, driven in part by changes in iBAT mitochondrial function.

Download Full-text

Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.248.5.e607 ◽

1985 ◽

Vol 248 (5) ◽

pp. E607-E617 ◽

Cited By ~ 6

Author(s):

J. G. Vander Tuig ◽

J. Kerner ◽

D. R. Romsos

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Heat Production ◽

Adult Rats ◽

Guanosine Diphosphate ◽

Bat Mitochondria ◽

Sympathoadrenal Activity ◽

Brown Adipose ◽

Energy Retention ◽

Ad Libitum

Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum-fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT.

Download Full-text

Heat production in the new-born rabbit and the fat content of the brown adipose tissue.

The Journal of Physiology ◽

10.1113/jphysiol.1965.sp007775 ◽

1965 ◽

Vol 181 (3) ◽

pp. 468-477 ◽

Cited By ~ 33

Author(s):

D Hull ◽

M M Segall

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Heat Production ◽

Fat Content ◽

New Born ◽

Brown Adipose

Download Full-text

Brown Adipose Tissue: Function and Physiological Significance

Physiological Reviews ◽

10.1152/physrev.00015.2003 ◽

2004 ◽

Vol 84 (1) ◽

pp. 277-359 ◽

Cited By ~ 3585

Author(s):

BARBARA CANNON ◽

JAN NEDERGAARD

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Heat Production ◽

Uncoupling Protein ◽

Sympathetic Nerves ◽

Physiological Significance ◽

Metabolic Efficiency ◽

Transfer Energy ◽

Brown Adipose ◽

Evolutionary Success

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 is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogen-esis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.

Download Full-text