Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss.

OBJECTIVE: Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool to prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose tissue (AT) expression of the genes involved in the regulation of lipolysis in obese subjects after WL. METHODS: Fifty-two obese subjects underwent weight-reducing dietary intervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program. RESULTS: AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS. However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. CONCLUSIONS: Excessive lipolysis may prevent an improvement in IS during WL. The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.

Intralipid/Heparin Infusion Alters Brain Metabolites Assessed With 1H-MRS Spectroscopy in Young Healthy Men.

Context: We previously demonstrated that insulin infusion altered metabolite concentrations in cerebral tissues assessed with proton magnetic resonance spectroscopy (1H-MRS) in young subjects with high insulin sensitivity, but not in those with low insulin sensitivity. Fat overload is an important factor leading to insulin resistance. Objective: The purpose of the current study was to examine the effect of elevated circulating free fatty acid (FFA) levels on metabolites in cerebral tissues assessed with 1H-MRS. Design: The study group comprised 10 young, healthy male subjects. 1H-MRS was performed at baseline and after 4-hour Intralipid (Fresenius Kabi)/heparin or saline infusions administered in random order. Voxels were positioned in the left frontal lobe, left temporal lobe, and hippocampus. The ratios of N-acetylaspartate (NAA), choline (Cho)-containing compounds, myo-inositol (mI), and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. Results: Intralipid/heparin infusion resulted in a significant increase in circulating FFAs (P < 0.0001). Significant changes in brain neurometabolite concentrations in response to Intralipid/heparin infusion were increases in frontal mI/Cr (P = 0.041) and mI/H2O (P = 0.037), decreases in frontal and hippocampal Glx/Cr (P = 0.018 and P = 0.015, respectively) and Glx/H2O (P = 0.03 and P = 0.067, respectively), and a decrease in hippocampal NAA/Cr (P = 0.007) and NAA/H2O (P = 0.019). No changes in neurometabolites were observed during the saline infusion. Conclusions: Acute circulating FFA elevation influenced cerebral metabolites in healthy humans and lipid-induced insulin resistance could be partly responsible for these effects.

The effect of moderate weight loss, with or without (1, 3)(1, 6)-ß-glucan addition, on subcutaneous adipose tissue inflammatory gene expression in young subjects with uncomplicated obesity.

PURPOSE: Obesity is characterized by insulin resistance and low-grade systemic and adipose tissue (AT) inflammation. It remains unclear whether beneficial effects of weight loss are related to AT inflammation. We aimed to assess the effect of weight loss during low-calorie diet on insulin sensitivity, AT expression of genes associated with inflammation in young subjects with obesity. Furthermore, we estimated the effects of immunomodulatory (1, 3)(1, 6)-ß-glucan (BG) on the above parameters. METHODS: The study group comprised 52 subjects with obesity. Twelve-week dietary intervention was applied, with randomization to receive or not 500 mg BG daily. Euglycemic hyperinsulinemic clamp, subcutaneous AT biopsy were performed before and after the program. Twenty normal-weight subjects, examined at baseline, served as a control group. RESULTS: At baseline, obese subjects had lower insulin sensitivity, lower AT ADIPOQ, JAK1, and JAK2 expression and higher AT expression of LEP, IL6ST, STAT3, MIF, CCL2, MMP9, and IL18. Forty obese subjects completed dietary intervention program, which resulted in 11.3% weight loss and 27% increase in insulin sensitivity (both p < 0.0001). AT IL6R, IL6ST, JAK1, and JAK2 expression increased, whereas MIF, CCL2, MMP9, and IL18 gene expression did not change in response to weight loss. BG addition had no effect on any of the parameters studied. CONCLUSIONS: Our data indicate that reduction in AT inflammation is not required for an improvement in insulin action during weight loss in subjects with uncomplicated obesity. BG does not have effects during dietary intervention.