Li-Fen Liu

Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus

BACKGROUND Weight loss may improve glucose control in persons with type 2 diabetes. The effects of fat quality, as opposed to quantity, on weight loss are not well understood. OBJECTIVE We compared the effects of 2 dietary oils, conjugated linoleic acid (CLA) and safflower oil (SAF), on body weight and composition in obese postmenopausal women with type 2 diabetes. DESIGN This was a 36-wk randomized, double-masked, crossover study. Fifty-five obese postmenopausal women with type 2 diabetes received SAF or CLA (8 g oil/d) during two 16-wk diet periods separated by a 4-wk washout period. Subjects met monthly with the study coordinator to receive new supplements and for assessment of energy balance, biochemical endpoints, or anthropometric variables. RESULTS Thirty-five women completed the 36-wk intervention. Supplementation with CLA reduced body mass index (BMI) (P = 0.0022) and total adipose mass (P = 0.0187) without altering lean mass. The effect of CLA in lowering BMI was detected during the last 8 wk of each 16-wk diet period. In contrast, SAF had no effect on BMI or total adipose mass but reduced trunk adipose mass (P = 0.0422) and increased lean mass (P = 0.0432). SAF also significantly lowered fasting glucose (P = 0.0343) and increased adiponectin (P = 0.0051). No differences were observed in dietary energy intake, total fat intake, and fat quality in either diet period for either intervention. CONCLUSIONS Supplementation with CLA and SAF exerted different effects on BMI, total and trunk adipose mass, and lean tissue mass in obese postmenopausal women with type 2 diabetes. Supplementation with these dietary oils may be beneficial for weight loss, glycemic control, or both.

Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice

Conjugated linoleic acid (CLA) induces insulin resistance preceded by rapid depletion of the adipokines leptin and adiponectin, increased inflammation, and hepatic steatosis in mice. To determine the role of leptin in CLA-mediated insulin resistance and hepatic steatosis, recombinant leptin was coadministered with dietary CLA in ob/ob mice to control leptin levels and to, in effect, negate the leptin depletion effect of CLA. In a 2 × 2 factorial design, 6 week old male ob/ob mice were fed either a control diet or a diet supplemented with CLA and received daily intraperitoneal injections of either leptin or vehicle for 4 weeks. In the absence of leptin, CLA significantly depleted adiponectin and induced insulin resistance, but it did not increase hepatic triglyceride concentrations or adipose inflammation, marked by interleukin-6 and tumor necrosis factor-α mRNA expression. Insulin resistance, however, was accompanied by increased macrophage infiltration (F4/80 mRNA) in adipose tissue. In the presence of leptin, CLA depleted adiponectin but did not induce insulin resistance or macrophage infiltration. Despite this, CLA induced hepatic steatosis. In summary, CLA worsened insulin resistance without evidence of inflammation or hepatic steatosis in mice after 4 weeks. In the presence of leptin, CLA failed to worsen insulin resistance but induced hepatic steatosis in ob/ob mice.

Maintenance of adiponectin attenuates insulin resistance induced by dietary conjugated linoleic acid in mice

Conjugated linoleic acid (CLA) causes insulin resistance and hepatic steatosis in conjunction with depletion of adipokines in some rodent models. Our objective was to determine whether the maintenance of adipokines, mainly leptin and adiponectin, by either removing CLA from diets or using an adiponectin enhancer, rosiglitazone (ROSI), could attenuate CLA-induced insulin resistance. Male C57BL/6 mice were consecutively fed two experimental diets containing 1.5% CLA mixed isomer for 4 weeks followed by a diet without CLA for 4 weeks. CLA significantly depleted adiponectin but not leptin and was accompanied by hepatic steatosis and insulin resistance. These effects were attenuated after switching mice to the diet without CLA along with restoration of adiponectin. To further elucidate the role of adiponectin in CLA-mediated insulin resistance, ROSI was used in a subsequent study in male ob/ob mice fed either control (CON) or CLA diet. ROSI maintained significantly higher adiponectin levels in CON- and CLA-fed mice and prevented the depletion of epididymal adipose tissue and the development of insulin resistance. In conclusion, we show that insulin resistance induced by CLA may be related more to adiponectin depletion than to leptin and that maintaining adiponectin levels alone either by removing CLA or using ROSI can attenuate these effects.

Hepatic steatosis by dietary-conjugated linoleic acid is accompanied by accumulation of diacylglycerol and increased membrane-associated protein kinase C ε in mice

SCOPE Conjugated linoleic acid reduces weight gain and adipose mass while inducing liver enlargement, hepatic steatosis, and insulin resistance in mice. The objective of this study was to determine if hepatic steatosis induced by conjugated linoleic acid would predict for hepatic diacylglycerol accumulation, increased membrane-associated protein kinase C ε, and hyperglycemia. METHODS AND RESULTS Six-wk-old C57Bl/6 male mice were fed a high-saturated fat diet for 3 wk and were then randomized to high-saturated fat diet with or without conjugated linoleic acid (1.5% wt). Following a 6-wk intervention, hepatic triacylglycerol, diacylglycerol, membrane-associated protein kinase C ε, and gluconeogenic gene expression were determined. Fasting glucose was determined at baseline and at the end of the study. Conjugated linoleic acid increased hepatic triacylglycerol and diacylglycerol concentration in association with increased membrane-associated protein kinase C ε. Diacylglycerol concentration proved to be a better predictor than triacylglycerol concentration for the change from baseline in fasting glucose concentration and final insulin concentration. The increase in diacylglycerol concentration was also associated with increased hepatic gluconeogenic gene expression in conjugated linoleic acid-treated animals. CONCLUSION Our data suggest that conjugated linoleic acid can initiate the pathophysiology responsible for hepatic insulin resistance. Additional studies are needed to determine if the accumulation of hepatic diacylglycerol by conjugated linoleic acid leads to hepatic insulin resistance.