7-day time study of lipid metabolism in normal and obese-hyperglycemic Bar Harbor mice. Qualitative and quantitative aspects

Abstract

1. Lipid metabo dism was fo llo wed fo r 7 days in Ican and o bese-hyperglyceniic 11-week o ld Bar Harb o r mice by measuring tiie inc o rp o rati o n o f a single d o se (90 fiC) o f [l-l^C] acétate in the liver and extrahepatic tissues. 2. In the liver of control animais, microsomes were more active (han supernatant with respect to lipogenesis at timc 10 min. They were also more efficient in desaturating lab elled 18 :0 than 16 : 0. A portion of unlal)eMed fatty acid was elongated with [l-WC] acétate. The radioactivity of liver glyccrides dccrcased rapidly b ecause of the sécrétion of lipoproteins rich in lab elled 18 : 1. The turnover at the 2-position in triglycérides remaining in the liver appeared to b e slower than at positions 1 and 3. 3. In the adipose tissue, the renewal of 1-2 diglycerides was very rapid. The lab elling of 1-3 diglycerides in this tissue suggests the existence of a monoglyceride pathway opcrative in niuo. Triglycérides were b etter lab elled in muscle than in adipose tissue. 4. In ail tissues, the secondary altérations in the structure of « precursor » triglycérides .ind phospholipids during the 7-day period indicate that a sizeab le proportion was su bmitted to either complète or partial lipolysis. Transfers of ''^C hy elongation and/or desaturation occurred in the newly relcased fatty acids b efore acyl rearrangements, as a resuit the divergences b etween distri b ution and lipid structures o b served at time 10 min were slowly reduced. 5. In ob ese-hyperglycemic mice twice as much of the radioactivity otïcred was incorporated into total b ody lipids. The liver was the chief lipogenetic site, with microsomes as well as supernatant overloaded with radioactive triglycérides. The microsomal 9,10 dehydrogenase was very active, and the 2-position of triglycérides was dominated b y la b elled 18 : 1 throughout the experiment. 6. Both, the renewal of adipose tissue 1-2 diglycerides and the radioactivity of muscle triglycérides were higher than in lean littermates.

Desaturation of stearic acid by liver and adipose tissue from obese-hyperglycaemic mice (ob/ob)

“…The results of the direct assay of stearic acid desaturase reported in this paper demonstrate that the increased incorporation of precursors into palmitoleic acid and oleic acid observed by Christophe's group in whole-tissue preparations from obese mice are due, at least in part, to an increase in the fatty acid desaturase system (Winand et al, 1968(Winand et al, , 1969a(Winand et al, , 1973. The threefold increase in the activity of stearic acid desaturase on a protein basis is similar to the increase in citrate cleavage enzyme (Komacker & Lowenstein, 1964) acetyl-CoA carboxylase and fatty acid synthetase (Chang et al, 1967) in livers from 12-week-old obese-hyperglycaemic mice compared with lean mice.…”

Lipolysis and cyclic AMP levels in epididymal adipose tissue of obese-hyperglycaemic mice

“…This hypothesis [43,44] will be further documented (in preparation). At any rate, the reduced hormone-stimulated lipolysis observed, in vitro, in obese-hyperglycaemic mice might suggest that in vivo, also, an impairment of lipolysis contributes to obesity, together with high local lipogenesis and a large influx of fatty acids of hepatic and dietary origin [45][46][47].…”

Hepatic ∆6-desaturase activity in lean and genetically obese ob/ob mice

“…The acyl-chain composition of membrane phospholipids is altered in obese (ob/ob) mice, the proportion of unsaturated fatty acids being increased in comparison with the membrane phospholipids of lean mice (Winand et al, 1973;Rouer et al, 1980;Hyslop et al, 1982;York et al, 1982;French et al, 1983). The activity of A9desaturase, the enzyme responsible for the desaturation of C16:0 and C18:0 fatty acids to C16:1 and C18:1 respectively, is increased in both liver and adipose tissue of obese mice (Enser, 1979;Enser & Roberts, 1982).…”