The association of β-catenin-dependent Wnt signaling with insulin resistance is tissue specific. Observed changes might reflect a compensatory mechanism to increase muscle glucose uptake and to generate new fat cells in insulin-resistant conditions.

Overweight/obesity is associated with altered expression of genes of adipogenesis, insulin signaling, ECM remodeling, and inflammation. NFκB seems to be the earliest inflammatory pathway altered at the transcriptional level in AT. Macrophages seem to be the first immune cells to infiltrate AT. Adipogenesis and ECM remodeling are the initial processes in AT that are independently associated with insulin sensitivity.

OBJECTIVEInsulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy (1H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity.RESEARCH DESIGN AND METHODSWe studied 16 healthy young men. 1H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity.RESULTSBaseline neurometabolic substrates were not different between the groups. Insulin infusion resulted in an increase in frontal NAA/Cr and NAA/H2O and frontal and temporal Glx/Cr and Glx/H2O and a decrease in frontal Cho/Cr and temporal Cho/H2O and myo-inositol/H2O (all P < 0.05, except temporal Glx/H2O, P = 0.054, NS) in the high-IS, but not in the low-IS, group. Insulin sensitivity correlated positively with frontal NAA/Cr and NAA/H2O and temporal Glx/H2O and negatively with temporal myo-inositol/Cr and myo-inositol/H2O assessed during the second 1H-MRS (all P < 0.05).CONCLUSIONSInsulin might influence cerebral metabolites, and this action is impaired in subjects with low whole-body insulin sensitivity. Thus, our results provide a potential link between insulin resistance and altered metabolism of the central nervous system.

These findings emphasize a significant iron accumulation in human skeletal muscle in association with obesity. The mechanisms implicated in these observations should be studied further.

PurposeObesity 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)-β-glucan (BG) on the above parameters.MethodsThe 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.ResultsAt 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.ConclusionsOur 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.