Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity.
High-fat, energy-dense diets promote weight gain and obesity in humans and other animals, but the mechanisms underlying such diet-induced obesity remain elusive. To determine whether a reduced capacity to oxidize fat is involved in the etiology of diet-induced obesity, we examined different measures of fatty acid oxidation in rats selectively bred for susceptibility (DIO) or resistance (DR) to dietary obesity before and after they were fed a high-fat diet and became obese. DIO rats eating a low-fat diet oxidized less dietary fatty acid in vivo and had lower levels of plasma ketone bodies during fasting compared with DR rats. Lean DIO rats fed a low-fat diet showed reduced liver messenger RNA expression of CD36, which transports fatty acids across cell membranes, and long-chain acyl-coenzyme A dehydrogenase (ACADL), which catalyzes the first step in the mitochondrial beta-oxidation of fatty acids. The deficit in CD36 and ACADL messenger RNA expression was also seen in obese DIO rats that had been eating a high-fat diet and, in addition, was accompanied by reduced expression of liver carnitine palmitoyl transferase I, the enzyme that mediates transport of long-chain fatty acids into mitochondria. No differences were found in the expression of liver enzymes involved in fat synthesis; however, in muscle, DIO rats fed the low-fat, but not high-fat, diet showed greater expression of diacylglycerol O-acyltransferase 1 and lipoprotein lipase than did DR rats. Expression of muscle enzymes involved in fatty acid oxidation was similar in the 2 groups. These findings provide a metabolic mechanism for the development of diet-induced obesity and thus suggest potential targets for intervention strategies to treat or prevent it.
Ji
Hong
H
Monell Chemical Senses Center, Philadelphia, PA 19104, USA.
Friedman
Mark I
MI
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000096:biosynthesis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens / Q000096:biosynthesis; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
D018955:CD36 Antigens; D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D012333:RNA, Messenger; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D051048:Diacylglycerol O-Acyltransferase; D008071:Lipoprotein Lipase