Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats

The mRNAs encoding mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (m tHMG-CoA synthase), the rate limiting enzyme in ketone body production, are highly expressed in subcutaneous (SC) and, to a lesser extent, in peri-epi didymal (PE) rat adipose tissues. This atypical mtHMG-CoA synthase gene exp ression is dependent on the age (from 9 weeks of age) and sex (higher in ma le than in female) of the rats. In contrast, the expression of mtHMG-CoA sy nthase in SC adipose deposit is independent of the nutritional state (fed v ersus starved) or of the thermic environment (24 degrees C versus 4 degrees C), The expression of mtHMG-CoA synthase is suppressed in SC fat pads of c astrated male rats whereas treatment of castrated rats with testosterone re stores a normal level of expression Moreover, testosterone injection induce s the expression mtHMG-CoA synthase in SC adipose tissue of age-matched fem ales. The presence of the mtHMG-CoA synthase immunoreactive protein con fer s to mitochondria isolated from SC adipose deposits, the capacity to produc e ketone bodies at a rate similar to that found iu liver mitochondria (SC = 13.7 +/- 0.7, liver = 16.4 +/- 1.4 nmol/min/mg prot), mtHMG-CoA synthase i s expressed in the stromal vascular fraction (SVF) whatever the adipose dep osit considered. While acetyl-CoA carboxylase (ACC) is only expressed in ma ture adipocytes, the other lipogenic enzymes, fatty acid synthase (FAS) and citrate cleavage enzyme (CCE), are expressed both in SVF cells and mature adipocytes, The expression of lipogenic enzyme genes is markedly reduced in adipocytes but not in SVF cells isolated from 48-h starved male rats. When SVF is subfractionated, mtHMG-CoA synthase mRNAs are mainly recovered in t wo fractions containing poorly digested structures such as microcapillaries whereas the lowest expression is found in the pre-adipocyte fraction. inte restingly FAS and CCE mRNAs co-segregate with mtHMG-CoA synthase mRNA, The possible physiological relevance of such atypical expression of mtHMG-CoA s ynthase is discussed. Atypical expression of mitochondrial 3-hydroxy-3-meth ylglutaryl CoA synthase in subcutaneous adipose tissue of male rats.