Summary
Carbohydrate and lipid metabolism has been studied in perfused livers of lean and obese-hyper-glycaemic(ob/ob) mice. The capacity for gluconeogenesis from lactate or pyruvate was similar in livers of both groups of mice. Incorporation of carbon from labelled pyruvate into hepatic lipids was much higher in livers ofob/ob mice than in those of lean controls. Total lipogenesis, as well as newly synthesized triglyceride secretion by perfused livers, was also estimated, by measuring3H (from3H2O) incorporation into total (i.e. liver + perfusate) and perfusate triglyceride fatty acids. Lipogenesis, both in the absence or in the presence of substrates, was greater in livers ofob/ob mice than in those of lean controls, as was newly synthesized triglyceride secretion. In the absence of oleate in the perfusate, the secretion of unlabelled triglyceride by livers of 06/06 mice was much higher than that of non-obese mice, but it did not increase further upon addition of oleate, as it did in livers of lean controls. Ketone body production by livers ofob/ob mice, perfused with albumin bound oleate, was considerably lower than that observed in control livers. Whenob/ob mice were made relatively insulin deficient by streptozotocin treatment, all these anomalies of lipid metabolism were restored towards normal. It is proposed that hyperinsulinaemia is responsible, at least in part, for the abnormalities in lipogenesis, triglyceride secretion and fatty acid oxidation to ketone bodies observed in livers of the obese-hyperglycaemic mice.
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This work has been supported by the Grant No 3.552.71 and No 3.8080.72 of the Fonds National Suisse de la Recherche Scientifique, Berne, Switzerland, and by a Grant-in-aid of Nestlé-Alimentana, Vevey, Switzerland.
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Assimacopoulos-Jeannet, F., Singh, A., Le Marchand, Y. et al. Abnormalities in lipogenesis and triglyceride secretion by perfused livers of obese-hyperglycaemic (ob/ob) mice: Relationship with hyperinsulinaemia. Diabetologia 10, 155–162 (1974). https://doi.org/10.1007/BF01219673
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DOI: https://doi.org/10.1007/BF01219673