Differences in transport of fatty acids and expression of fatty acid transporting proteins in adipose tissue of obese black and white women.

We have reported that the rate of de novo triglyceride (TG) synthesis by omental, but not subcutaneous, adipose tissue was higher in African-American women (AAW) than in Caucasian women (CAW). The purpose of this study was to explore the potential mechanisms underlying this increase. Toward that end, we determined the activities of key enzymes in the pathway of TG synthesis, the rates of uptake of fatty acids by adipocytes, mRNA and protein levels of the fatty acid-transporting proteins FAT/CD36 and FATP, and mRNA and protein levels of PPARgamma in omental fat of AAW and CAW. The results showed 1) no difference in the activity of phosphofructokinase, glycerol-3-phosphate dehydrogenase, or diacylglycerol acyltransferase; 2) a higher rate of fatty acid uptake by adipocytes of the AAW; 3) an increase in the mRNA and protein levels of CD36 and FATP4 in the fat of the AAW; and 4) an increase in the mRNA and protein levels of PPARgamma, which can stimulate the expression of CD36 and FATP. These results suggest that the increase in the transport of fatty acid, which is mediated by the overexpression of the transport proteins in the omental adipose tissue of the AAW, might contribute to the higher prevalence of obesity in AAW.

Ketone body metabolism in lean and obese women.

Previous studies have demonstrated decreases in whole-body and muscle fat oxidation in obese individuals. Because muscle also uses ketone bodies, and because the ketone body oxidation pathway differs from that of fatty acid oxidation, this study was initiated to determine whether there were differences in ketone body metabolism between obese and lean subjects. Plasma beta-hydroxy-butyrate (beta-OHB) concentration was measured in 47 lean and 47 age-matched obese women, and the rate of beta-OHB oxidation by muscle homogenates was measured in a subset of 8 lean and 8 obese women. Plasma free fatty acid levels, which have been reported to correlate with ketone body production, were higher (P<.05) in the obese than in the lean women (662+/- 46 and 463+/- 44 nmol/L, respectively) as was plasma insulin level. However, the beta-OHB concentration was lower in obese than in lean subjects (235+/-17 and 323+/-29 micromol/L, respectively; P<.05). The rate of beta-OHB oxidation was also lower (P<.05) in muscle of the obese than that of the lean group (139.6+/-12.6 vs 254.6+/-30.0 nmol of CO(2) produced per gram of tissue per hour). These data illustrate that production and use of ketone bodies are lower in obese women than in lean controls. The decreased oxidation of ketone bodies by muscle is consistent with aberrations in muscle metabolism in the obese individuals that most likely relates to a decrease in mitochondrial numbers.

Suppression of hepatic cholesteryl ester transfer protein expression in obese humans with the development of type 2 diabetes mellitus.

Cholesteryl ester transfer protein (CETP) is a plasma enzyme that can modulate the profile of lipoproteins and is thus considered: 1) a mediator of vascular disease; and 2) a therapeutic target for vascular disease. In the present study, we pursued a better understanding of the effect of type 2 diabetes on the expression of CETP in obese patients. Obesity was accompanied by a 20% elevation in plasma CETP that was eliminated with the development of diabetes. These differences were observed for both men and women and were due to variations in the amount of CETP protein in the plasma. The mRNA and protein of both the full-length (CETPFL) and alternatively spliced (CETPDelta9) forms of CETP were lower in the liver, but not in either sc or omental adipose tissue depots, of diabetic obese subjects. Sterol response element binding proteins 1 and 2 were also lower in liver homogenates, suggesting that these transcription factors may mediate the effects of type 2 diabetes on hepatic CETP expression. Thus, the suppressive effects of type 2 diabetes in obese subjects are observed in both men and women and may be due, at least in part, to a suppression of hepatic CETP expression.

Ethnic differences in adiponectin levels.

Adiponectin levels were measured in African American and Caucasian women of varying body mass index (BMI). Plasma adiponectin levels were compared and the relationship between adiponectin and insulin sensitivity was assessed. Adiponectin levels were similar in the Caucasian obese (7.0 +/- 0.8 microg/mL), African American obese (7.3 +/- 3.5 microg/mL), and African American non-obese women (7.1 +/- 1.2 microg/mL), but were significantly higher in Caucasian non-obese women (12.2 +/- 1.4 microg/mL). Correlational analyses demonstrated that BMI, insulin, and homeostasis model assessment (HOMA) correlated significantly with adiponectin levels in only the Caucasian women. These results provide support for the notion that what applies to other ethnic populations might not apply to the African American population, and that the association between adiponectin and insulin sensitivity needs to be clarified in the African American population.

Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and white American women.

The purpose of this study was to determine if there were differences in the capacity of skeletal muscle from morbidly obese Black and White American women to oxidize fatty acids. The oxidation rates of (14)C-palmitate, (14)C-palmitoyl-CoA, and (14)C-palmitoyl-carnitine were measured in whole homogenates of rectus abdominus from Black and White women who were similar in age and body mass index (BMI). The activities of muscle citrate synthase (CS), beta-hydroxy acyl-CoA dehydrogenase (beta-HAD), and mitochondrial and microsomal acyl-CoA synthetase (ACS) were measured in the 2 groups. The results showed that the rate of (14)C-palmitate oxidation by muscle of Black women was 25% that of Whites (8.7 +/- 1.5 v 34.4 +/- 6.8 nmol (14)CO(2) produced/gram tissue wet weight/ hour; P <.05), but the rates of (14)C-palmitoyl-CoA and (14)C-palmitoyl-carnitine oxidation were not different in the 2 groups. No differences were found in the activities of CS or beta-HAD. However, the activities of both mitochondrial and microsomal ACS were lower in the Black women than the Whites (mitochondrial ACS 25.1 +/- 3.9 v 36.4 +/- 5.0 nmol/mg protein/min; P <.05; microsomal ACS 6.2 +/- 0.5 v 8.5 +/- 0.5; nmol/mg protein/min; P <.005). The lower rate of palmitate oxidation, and the lack of differences in the rates of palmitoyl-CoA and palmitoyl-carnitine oxidation indicate that there is a defect in the activation of the fatty acid in the muscle of the Black women. This was confirmed by the decrease in mitochondrial ACS activity in the Black women. The decreased fatty acid oxidation by skeletal muscle of obese Black women could result in shunting these fuels from muscle to adipose tissue for storage, which may contribute to the maintenance of obesity in the Black women.

Cholesteryl ester transfer protein expression prevents diet-induced atherosclerotic lesions in male db/db mice.

OBJECTIVE: Accompanying more atherogenic lipoprotein profiles and an increased incidence of atherosclerosis, plasma cholesteryl ester transfer protein (CETP) is depressed in diabetic obese patients compared with nondiabetic obese counterparts. The depressed levels of CETP in the plasma of diabetic obese individuals may contribute to the development of an atherogenic lipoprotein profile and atherogenesis. We have examined the effect of CETP expression on vascular health in the db/db model of diabetic obesity. METHODS AND RESULTS: Transgenic mice expressing the human CETP minigene were crossed with db/db strain, and 3 groups of offspring (CETP, db, and db/CETP) were placed on an atherogenic diet for 16 weeks. The proximal aorta was then excised and examined for the presence of atherosclerotic plaques. In db mice, 9 of 11 had intimal lesions with a mean area of 26 098+/-7486 microm2. No lesions greater than 1000 microm2 were observed in db/CETP or CETP mice. CETP-expressing mice had lower circulating cholesterol concentrations than db mice. Fractionating plasma lipids by FPLC indicated that the difference in total cholesterol was primarily attributable to differences in VLDL and LDL. CONCLUSIONS: The expression of human CETP in db/db mice prevented the formation of diet-induced lesions, suggesting an antiatherogenic effect of CETP in the context of diabetic obesity.

Muscle fiber type is associated with obesity and weight loss.

The purpose of this study was to test the hypothesis that muscle fiber type is related to obesity. Fiber type was compared 1) in lean and obese women, 2) in Caucasian (C) and African-American (AA) women, and 3) in obese individuals who lost weight after gastric bypass surgery. When lean (body mass index 24.0 +/- 0.9 kg/m(2), n = 28) and obese (34.8 +/- 0.9 kg/m(2), n = 25) women were compared, there were significant (P < 0.05) differences in muscle fiber type. The obese women possessed fewer type I (41.5 +/- 1.8 vs. 54.6 +/- 1.8%) and more type IIb (25.1 +/- 1.5 vs. 14.4 +/- 1.5%) fibers than the lean women. When ethnicity was accounted for, the percentage of type IIb fibers in obese AA was significantly higher than in obese C (31.0 +/- 2.4% vs. 19.2 +/- 1.9%); fewer type I fibers were also found in obese AA (34.5 +/- 2.8% vs. 48.6 +/- 2.2%). These data are consistent with the higher incidence of obesity and greater weight gain reported in AA women. With weight loss intervention, there was a positive relationship (r = 0.72, P < 0.005) between the percentage of excess weight loss and the percentage of type I fibers in morbidly obese patients. These findings indicate that there is a relationship between muscle fiber type and obesity.

Ethnic differences in postprandial triglyceride response to a fatty meal and lipoprotein lipase in lean and obese African American and Caucasian women.

The purpose of this study was to determine if there were differences in the expression of lipoprotein lipase (LPL) in African American (AA) and Caucasian (CA) women. LPL mRNA and protein levels were determined in subcutaneous and omental fat of lean and obese subject from the 2 races (4 groups; 12 to 15 subjects/group). LPL mRNA levels of lean AA were not different from the lean CA women in either fat depot. LPL mRNA levels in the subcutaneous fat of the obese AA were higher than those of CA women (1.3 +/- 0.1 v 0.86 +/- 0.06, P.05), but not different in omental fat. LPL mass in subcutaneous fat of lean AA was higher (0.95 +/- 0.09 v 0.64 +/- 0.06, P.05), but not different in omental fat from the CA women. LPL mass in subcutaneous and omental fat was not different in the 2 obese groups. Differences in the activity of LPL were evaluated by (1) measuring the increments of triglycerides (TG) at 2, 4, 6, and 8 hours after a fat-rich meal and (2) by measuring postheparin plasma lipolytic activity. Plasma TG levels in the lean AA were lower than those of the lean CA women at basal and at 2, 4, 6, and 8 hours postprandially. The increase in TG levels at 2 hours tended to be lower in the AA than the CA women, was significantly lower at 4 hours (24 +/- 5 v 45 +/- 7, P.05), and was not different 8 hours postprandially. No differences were observed in either the absolute or the incremental concentrations of TG in the obese groups. Postheparin plasma LPL activity was higher in the lean AA than the lean CA women (4.8 +/- 0.4 v 3.4 +/- 0.4, P.05), but not different in the obese groups. These results indicate that the lower TG concentrations in the lean AA women may be partly due to enhanced expression, activity, and intravascular availability of LPL. Furthermore, it appears that the racial differences in expression and function of LPL are attenuated with obesity.