Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

Abstract

Obesity (BMI C30 kg/m 2 ) increases the risk of developing lifestyle-related diseases. A subgroup of obese individuals has been described as ''metabolically healthy, but obese'' (MHO). In contrast to at-risk obese (ARO), the MHO phenotype is defined by a favourable lipid profile and a normal or only slightly affected insulin sensitivity, despite the same amount of body fat. The objective was to characterize the metabolic phenotype of MHO subjects. We screened a variety of genes involved in lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC). Obese subjects (men and women; 18-70 years) with BMI C30 kg/m 2 were characterized as MHO (n = 9) or as ARO (n = 10). In addition, eleven healthy, normal weight subjects characterized as healthy by the same criteria as described for the MHO subjects were included. We found that with similar weight, total fat mass and fat mass distribution, the ARO subjects have increased plasma levels of gamma-glutamyl transpeptidase and free fatty acids. This group also has altered expression levels of a number of genes linked to lipid metabolism in PBMC with reduced gene expression levels of uncoupling protein 2, hormone-sensitive lipase and peroxisome proliferatoractivated receptor d compared with MHO subjects. The present metabolic differences between subgroups of obese subjects may contribute to explain some of the underlying mechanisms causing the increased risk of disease among ARO subjects compared with MHO subjects.

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

“…In agreement with our findings, no differences in the expression of inflammatory genes in adipose tissue or PBMC between metabolically obese healthy and metabolically abnormal obesity groups have been found in recent studies (Catalán et al 2007a;Gómez-Ambrosi et al 2014;Telle-Hansen et al 2013). Moreover, we have identified that the upregulation of gene expression levels of most of the novel adipokines in PBMC is associated with their circulating concentrations, suggesting the contribution of these types of cells to the increased circulating levels in obesity states.…”

Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health

“…Its action has also been suggested to be linked with insulin secretion and insulin action (Kraemer and Shen 2002). Expression of this gene has also been described in PBMCs, where its level was found to be reduced in ''at risk'' obese subjects (Telle-Hansen et al 2013). Interestingly, in the present study, we show that young CR animals exhibited higher Lipe mRNA levels in PBMCs and similarly in iWAT.…”

Serum fatty acid profiling within distinct lipid fractions provides a more robust indicator of insulin resistance in humans than total triglyceride and fatty acid profiles

“…Adiponectin is a protein produced by adipose tissue and has known insulin--sensitizing [283] and anti--inflammatory [7] properties. Our adiponectin results are similar to those reported by Telle--Hansen et al, who had an equivalently sized cohort and used similar classification criteria to identify MHO individuals [273]. However, our findings do not agree with those of other studies showing that MHO individuals had higher adiponectin levels compared to MUO individuals [284--288].…”

“…While such an approach has not been used to study MHO, this is warranted given that the expression of lipogenic genes was recently shown to differ between MHO and MUO individuals [273]. As such, we expect that using a FA profiling approach will generate novel insight to help understand if FAs contribute to the reduced inflammatory state seen in MHO individuals.…”