Rosiglitazone decreases intra- to extramyocellular fat ratio in obese non-diabetic adults with metabolic syndrome.

BACKGROUND: Insulin resistance is intrinsically related to intramyocellular (IMCL) rather than extramyocellular (EMCL) triglyceride content. Conflicting results have been reported on the ability of insulin sensitizer agents, such as thiazolidinediones, to modify muscle fat distribution. The aim of this study was to investigate the role of rosiglitazone on muscle fat compartment distribution in an adult population of obese non-diabetic metabolic syndrome patients. PATIENTS AND METHODS: Fifteen obese, non-diabetic, metabolic syndrome patients were studied by means of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy before and after treatment with rosiglitazone 8 mg/day for 6 months. Anthropometrical and metabolic variables were assessed. RESULTS: After rosiglitazone, body weight and hip circumference increased [100.9 (91.12-138.7) vs. 107.0 (79.6-142.8) kg and 118 (107-126) vs. 122 (110-131) cm]; while waist-hip ratio (WHR) decreased from 0.93 (0.87-1.00) to 0.89 (0.82-0.97) (P < 0.001 for all). Additionally, fasting plasma glucose, insulin and homeostatis model assessment of insulin resistance (HOMA-IR) significantly decreased while adiponectin increased over threefold [9.7 (3.7-17.7) vs. 38.0 (19.3-42.4) microg/ml] without any changes in resistin. Finally, the IMCL did not change [267.54 (213.94-297.94) vs. 305.75 (230.80-424.75) arbitrary units (AU), P = 0.15] while the EMCL increased [275.53 (210.39-436.66) vs. 411.39 (279.92-556.59) AU; P < 0.01] therefore decreasing the IMCL-to-EMCL (IMCL/EMCL) ratio [1.07 (0.78-1.23) vs. 0.71 (0.53-0.96); P < 0.01]. CONCLUSION: Rosiglitazone treatment increased body weight and hip circumference and decreased WHR. More importantly, it decreased the IMCL/EMCL ratio by increasing the EMCL without any significant change on the IMCL.

Adiponectin is related to intramyocellular lipid content in non-diabetic adults.

OBJECTIVE: Insulin resistance (IR) is associated with intramyocellular lipid (IMCL) content and low serum adiponectin (ADP) levels and ADP is also involved in muscle fat oxidation. However, the relationship between ADP and IMCL content is still controversial and in this study we explored it further in non-diabetic adults. DESIGN: Cross-sectional clinical study. SUBJECTS: Thirty-three adult subjects, 24 obese non-diabetic patients with metabolic syndrome (MS) and 9 lean healthy controls. MEASUREMENTS: Proton nuclear magnetic resonance spectroscopy (1H-NMRS) was performed to quantify IMCL content. The latter plus serum ADP, anthropometrics and biochemical parameters were evaluated and compared in these 2 groups. RESULTS: MS patients had higher body mass index, waist, waist-to- hip ratio, glucose, insulin, and triglycerides and lower HDL cholesterol (HDLc) compared to controls. Homeostasis model assessment of IR (HOMA-IR) [3.25 (2.58-4.13) vs 1.02 (0.73- 1.29); p<0.0001] and IMCL content [266.1 (189.9-296.3) vs 72.85 (55.3-109.4) AU, p<0.0001] were higher, and quantitative insulin-sensitivity check index (QUICKI) [0.32 (0.31-0.33) vs 0.38 (0.37-0.40); p<0.0001] and ADP [8.6 (4.05-15.95) vs 21.1 (12.9- 24.4) microg/ml; p=0.02] were lower in MS subjects compared to controls. IMCL content was directly associated to glucose, insulin, triglycerides, and HOMA-IR and inversely to HDLc, QUICKI and, more importantly, to ADP (r=-0.41; p<0.05). Only in the MS group, ADP partially influenced IMCL content. CONCLUSION: ADP is inversely related to IMCL content in non-diabetic adults. This finding has possible implications for the role of ADP in muscle fat oxidation, IR, and MS.