Raising at thermoneutrality prevents obesity and hyperphagia in
brown adipose tissue-ablated transgenic mice.
Melnyk, Anna, Mary-Ellen Harper, and Jean Himms-Hagen.
Department of Biochemistry, University of Ottawa, Ottawa, Ontario
K1H 8M5, Canada
APStracts 3:0405R, 1996.
Melnyk, Anna, Mary-Ellen Harper, and Jean Himms-Hagen. Raising at
thermoneutrality prevents both obesity and hyperphagia in brown
adipose tissue (BAT)-ablated transgenic mice. Am. J. Physiol.
(Regulatory Integrative Comp. Physiol. ): Transgenic mice with
ablation of brown adipocytes induced by brown adipocyte-specific
expression of diphtheria toxin A-chain (DTA) driven by the uncoupling
protein (UCP) promoter (UCP-DTA mice) become obese and hyperphagic
(Lowell et al., Nature, Lond. 366: 740-742, 1993). A deficit in
energy expenditure for brown adipose tissue (BAT) thermogenesis in
these mice is presumed to contribute to the development of obesity.
The objective of the present study was to obviate any deficit in BAT
thermogenesis by raising transgenic and control mice at
thermoneutrality (35 degrees C), where both would have equally
inactive BAT, to see whether this would prevent the obesity and the
hyperphagia. Transgenic and control mice were raised from weaning (3
weeks of age) to 8 weeks of age at either 24 degrees C or 35 degrees
C. Raising at 35 degrees C completely prevented development of
obesity of UCP-DTA mice, as indicated by their normal carcass fat,
normal weights of four major white adipose tissue depots and normal
size of white adipocytes. As seen before, transgenic mice raised at
24 degrees C had excess weight gain by 6 weeks of age and by 8 weeks
had doubled carcass fat, an obesity characterized by increased white
adipocyte size with no increase in number of adipocytes. The
treatment also prevented hyperphagia of UCP-DTA mice, consistent with
the hypothesized role of BAT thermogenesis in control of
thermoregulatory feeding (Himms-Hagen, Proc. Soc. Exp. Biol. Med.
208: 159-169, 1995). UCP-DTA mice thus differ from genetically obese
mice (ob/ob, db/db) for which raising at thermoneutrality is known
not to prevent either the obesity or the hyperphagia. Both the
obesity and the hyperphagia of UCP-DTA mice appear to be due to their
deficit in BAT thermogenesis.
Received 7 June 1996; accepted in final form 23 October 1996.
APS Manuscript Number R324-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996