Binding of guanine nucleotides to the outer surface of the inner membrane of guinea pig brown fat mitochondria in correlation with the thermogenic activity of the tissue

Reports on a reciprocal relationship between sympathetic-nerve and experimentally induced changes in thyroid-hormone activity called into question the proposed role of thyroxine in the changes seen in the brown fat after cold adaptation. Rats reared at +30, +22, and +5 degrees C received daily injections of thyroxine (1 mg/kg). After 3 wk of treatment, the thermogenic state of the tissue was assessed by measuring the capacity of the brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). GDP-inhibited mitochondrial swelling, brown adipose tissue (BAT) wet weights, and mitochondrial yields were also measured. The control animals showed a linear increase in GDP binding between +30 and +5 degrees C. Thyroxine was found to lower the GDP binding markedly at +5 degrees C, less so at +22 degrees C, while no effect was evident at +30 degrees C. The values at +22 and +30 degrees C were identical. The other parameters studied all confirmed these results. The conclusion made is that the thyroxine-induced rise in basal metabolic rate lowers the critical temperature and reduces the demand for nonshivering thermogenesis. This is reflected in the reduced GDP binding and hence heating capacity of the brown fat mitochondria.

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Influence of subdiaphragmatic vagotomy and brown fat sympathectomy on thermogenesis in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.3.e239 ◽

1985 ◽

Vol 249 (3) ◽

pp. E239-E243 ◽

Cited By ~ 1

Author(s):

P. L. Andrews ◽

N. J. Rothwell ◽

M. J. Stock

Keyword(s):

Insulin Treatment ◽

Brown Fat ◽

Guanosine Diphosphate ◽

Subdiaphragmatic Vagotomy ◽

Brown Adipose ◽

Adrenergic Antagonist ◽

Brown Adipose Tissue Activity ◽

Acute Injection ◽

Brown Fat Mitochondria ◽

Thermogenic Response

Infusion of rats with insulin (8 U/day via implanted minipump) for 7 days caused a 22% rise in resting oxygen consumption, which was inhibited by acute injection of the beta-adrenergic antagonist propranolol. Insulin treatment produced significant increases in brown fat mass, protein content, and total thermogenic activity (assessed from binding of guanosine diphosphate to isolated brown fat mitochondria), but these responses were inhibited by prior surgical sympathectomy of the tissue. Animals subjected to subdiaphragmatic vagotomy gained more weight than pair-fed, sham-operated controls and showed reductions in total energy expenditure, the acute thermogenic response to a meal and brown adipose tissue activity. Daily injections of insulin (1 U/day) prevented all of these effects of vagotomy. These data demonstrate that the changes in brown fat activity induced by exogenous insulin are mediated by the sympathetic nervous system and that the depressed thermogenesis and brown fat activity associated with vagotomy appear to be due to a relative insulin deficiency and can be reversed by treatment with the hormone.

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