Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats

Dec 1, 1981Metabolism: clinical and experimental

Differences in fat, sugar storage, and sugar creation by liver cells from lean and obese Zucker rats

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Abstract

Hepatocytes from obese rats exhibited greater rates of fatty acid synthesis and glucose utilization but produced less ketone bodies compared to lean rats.

Obese rat hepatocytes accumulated more lactate and pyruvate from glycogen stores than those from lean rats.
Lipogenesis in hepatocytes from obese rats showed reduced sensitivity to inhibition by dibutyryl cyclic AMP (DBcAMP).
Glycogenolysis was similarly stimulated by DBcAMP in both obese and lean rat hepatocytes.
Hepatocytes from starved obese rats retained glycogen and showed detectable lipogenesis, unlike starved lean rats.
Hepatocytes from lean rats exhibited faster gluconeogenesis rates than those from starved obese rats.

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Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.

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Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats

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