Intermediary metabolism during the development of obesity and diabetes in the desert rodent Acomys cahirinus.
The spiny mouse Acomys cahirinus, which exhibits beta-cell hyperplasia but low insulin secretion in captivity responded with hyperlipidemia without obesity or diabetes on a sucrose diet and became obese, and glucose-intolerant on a diet of fat-rich seeds. A three-month sucrose diet induced a marked rise in the activity of regulatory enzymes of glycolysis and lipogenesis in the liver but not in adipose tissue. There was also increased energy waste on this diet evident from a three-fold rise in the activity of hepatic mitochondrial FAD-glycerophosphate oxidase associated with an elevation in circulating triodothyronine. The obesity in mice maintained for three months on fat rich seeds was associated with moderate hyperglycemia, mild hyperinsulinemia and little change in circulating lipids. There was a decrease in the activity of glycolytic and lipogenic enzymes both in the liver and adipose tissue. Adipose tissue lipoprotein lipase activity rose, suggesting that the chylomicrons carrying the exogenous fat were better assimilated than the very-low-density lipoproteins synthesized from the dietary carbohydrate. Along with adipose tissue gain, triglyceride deposition was apparent in several muscles, accompanied by increased tissue free fatty acid, citrate and glycogen content. This suggested relation of increased muscle fat utilization with decreased glucose metabolism and insulin sensitiveness. Diverse responses to diets were thus elicited, which were particularly discernible in desert animals surviving on a limited caloric intake. Detailed follow up of these enzymatic and endocrine adaptation patterns to selective nutritional affluence may promote the understanding of the mechanisms leading to hyperlipidemia with leanness and normal glucose homeostasis versus obesity with diabetes but without hyperlipidemia.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009115:Muridae; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D013963:Thyroid Hormones / Q000378:metabolism
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D013963:Thyroid Hormones; D013395:Sucrose