Studies of the Metabolic Effects Induced in the Rat by a High Fat Diet - II. Disposal of Orally Administered (14C)-Glucose*

Abstract

(6_ 14 C) glucose (1.5-2 gm/kg body weight) was administered orally to fasted rats fed for five weeks from weaning a fat or a carbohydrate synthetic diet. Rats were killed by deca-PAtation at 30, 60, 120 and 180 minutes after the load. ein the gut, glucose (6-14 C) glucose and insulin in the serum, glycogen and (1~C) glycogen in the liver, were measured. Fat-adapted rats exhibited impaired glucose tolerance and sensitivity to endogenous insulin which resulted in higher levels of exogenous glucose in the serum and in some slackening of disposal of the load by the tissues. An altered r~ lease of glucose by the liver does not seem to be a major factor of hyperglycaemia in these conditions. The level of liver glycogen before the load and throughout the experiment is higher in the fat group. As in the contral group, hepatic glycogen synthesis after glucose administration develops linearly between 30 and 120 minutes without any evident relation to the time variation of the level and the specific radioactivity of serum glucose. In addition, the specific activity of glycogen stabilized to a value much low• er than that of the load glucose. After fat diet, a significant reduction of the amount of 14 carbon incorporated into liver glycogen was observed which can contribute to the decrease of tolerance to orally administered glucose.

In-vitro and In-vivo Responsiveness of Muscle and Adipose Tissue to Insulin in Rats Rendered Obese by a High-fat Diet

“…It is clear from the present study that a high-fat diet exerts a further inhibition at the level of fatty acid synthesis, which, although a minor pathway in this tissue, is yet the most strongly inhibited. Consistent with the in-vitro finding, [6][7][8][9][10][11][12][13][14] Cj glucose incorporation into diaphragm glycogen in vivo is unaltered by a high-fat diet.…”

“…l l isoenzyme) activity. 17 Measuring the metabolism of [6][7][8][9][10][11][12][13][14] Cj glucose shows that each pathway is specifically'regulated by the nutritional conditions. A high-fat diet most strongly depresses fatty acid synthesis.…”

“…Similarly, the strong depression of fatty acid synthesis is well correlated with the striking decrease of lipogenic enzyme activities described in the adipose tissue of high-fat-fed rats. 1 2 0 It is of interest that the partition of labeled carbon from' [6][7][8][9][10][11][12][13][14] Cj glucose between glycerol and fatty acid moieties of glycerides depends greatly upon the experimental conditions. In both groups of rats, the fatty-acid-to-glycerol ratio is much higher in vitro than in vivo.…”

In vivo insulin resistance in individual peripheral tissues of the high fat fed rat: assessment by euglycaemic clamp plus deoxyglucose administration

“…Previous studies in man have suggested that a diet high in fat content leads to reduced glucose tolerance [1, 21. Glucose intolerance can also be induced by short-term feeding of a high fat diet to the laboratory rat [3][4][5], and further in vitro studies [6][7][8][9] would suggest that the glucose intolerance is mediated, at least in part, by resistance to insulin action in peripheral tissues. However, neither the tissue specificity of insulin resistance nor the magnitude of impairment at the whole body level have been identified.…”

Developmental Changes in Histone macroH2A1-Mediated Gene Regulation

“…We believe that this sexual dimorphism may reflect a difference in the responses of females and males to increased delivery of fatty acids to the liver. Previous studies of the effects of increased fatty acid delivery on liver insulin resistance have been done on male mice and rats (18,19,34), suggesting that the responses of females may be different.…”