Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes.
Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Barakat
H A
HA
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858-4354.
McLendon
V D
VD
Carpenter
J W
JW
Marks
R H
RH
Legett
N
N
O'Brien
K
K
Caro
J F
JF
D000328:Adult; D002469:Cell Separation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D005989:Glycerides / Q000096:biosynthesis; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium; D014867:Water / Q000378:metabolism
D005989:Glycerides; D008055:Lipids; D014867:Water; D014316:Tritium