Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats

Journal Article · Thu Jan 01 04:00:00 EST 1981 · Metabolism; (United States)

DOI:https://doi.org/10.1016/0026-0495(81)90060-3· OSTI ID:5639392

Triscari, J; Greenwood, M R; Sullivan, A C

Fatty acid synthesis and CO/sub 2/ production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of /sup 3/H/sub 2/O, and several carbon precursors. The incorporation of /sup 3/H/sub 2/O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of /sup 3/H/sub 2/O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO/sub 2/ production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO/sub 2/ production from /sup 3/H/sub 2/O and (U-/sup 14/C)glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.

• Research Organization: Department of Pharmacology II, Roche Research Center, Hoffmann-La Roche Inc. Nutley, NJ
• OSTI ID: 5639392
• Journal Information: Metabolism; (United States), Journal Name: Metabolism; (United States) Vol. 30:11; ISSN MTBMA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BODY
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CHALCOGENIDES
CHOLESTEROL
DIGESTIVE SYSTEM
GLANDS
GLUCAGON
GLUCOSE
HEXOSES
HORMONES
HYDROXY COMPOUNDS
INSULIN
LABELLED COMPOUNDS
LIPIDS
LIVER
MAMMALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
RATS
RODENTS
SACCHARIDES
STEROIDS
STEROLS
SYNTHESIS
TRITIUM COMPOUNDS
VERTEBRATES