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Aim: This study looked at the association of adipokines, inflammatory and oxidative stress markers in subjects with the following phenotypes: metabolically healthy, nonobese (MHNO), metabolically healthy, obese (MHO), metabolically obese, nonobese (MONO), and metabolically obese, obese (MOO)., Materials and Methods: Subjects with MHNO (n=462), MHO (n=192), MONO (n=315), and MOO (n=335) were randomly selected from the Chennai Urban Rural Epidemiology Study. Adiponectin, visfatin, resistin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), oxidized low-density lipoprotein (LDL), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay., Results: Levels of adiponectin were lowest in the MOO group, followed by the MONO, MHO, and the MHNO groups (P=0.042), whereas the levels of visfatin (P=0.042) and resistin (P=0.043) were highest in the MOO group, followed by the MONO, MHO, and the MHNO groups. Levels of hs-CRP (P=0.029), TNF-α (P=0.036), IL-6 (P=0.042), oxidized LDL (P=0.036), and MCP-1 (P=0.039) increased from the MHNO to MHO to MONO to MOO phenotypes. Linear regression analysis of the parameters with body mass index (BMI) and metabolic syndrome components showed that adiponectin is negatively associated with abdominal obesity (β=-0.060; P=0.039) and BMI (β=-0.076; P=0.009) and that TNF-α is negatively associated with high-density lipoprotein levels (β=0.114, P=0.049) even after adjusting for age and gender. hs-CRP (β=0.112, P=0.020) and oxidized LDL (β=0.114, P=0.050) showed a positive association with systolic blood pressure even after adjusting for age and gender., Conclusions: The metabolically obese phenotype is characterized by altered adipokine and inflammatory profiles, which could make this phenotype at high risk for type 2 diabetes mellitus and cardiovascular diseases.

Even after successful weight reduction, obese adults tend to quickly regain the lost weight. This raises the question of whether weight loss improves the underlying chronic adipose tissue inflammation characteristic of obesity. In order to improve our understanding of the mechanisms that reshape metabolic organs during weight loss, we investigated the macrophage and T cell function of the liver and adipose tissue on reversing high fat diet (HFD) mice to normal control diet (NCD). Obese mice that were switched to NCD showed an improvement in their metabolic profile that included enhanced glucose and insulin tolerance, decreased cholesterol, triglyceride, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) levels that were comparable to NCD controls. However, despite weight loss, increased frequencies, but not total numbers, of IL-17+ and IL-22+ CD4+ T cells, IFN-γ+ and TNF+ CD8+ T cells and IL-17+ and IL-22+ CD8+ T cells were observed in the adipose tissue of mice switched from HFD to NCD compared to NCD and even HFD fed mice. Further, in the liver, IFN-γ+ and TNF+ CD8+ T cell, IL-17+ and IL-22+ CD8+ T cell, macrophage frequencies and their expression of antigen presenting molecules were increased. To determine if macrophages are the major determinants of the sustained inflammation observed during weight loss, we depleted macrophages, which significantly reduced IFN-γ+, TNF+, IL-17+, and IL-22+ CD8+ T cell frequencies in the liver and the adipose tissue. In conclusion, we show that although weight loss improves the metabolic profile, there is an active and ongoing CD8+ T cell inflammation in liver and adipose tissue mediated by macrophages.

Compared to the innate immune system, the contribution of the adaptive immune response during obesity and insulin resistance is still not completely understood. Here we demonstrate that high fat diet (HFD) increases the frequencies of activated CD4+ and CD8+ T cells and frequencies of T cells positive for IFN-γ and IL-17 in the adipose tissue. The adipocyte-derived soluble factor adiponectin reduces IFN-γ and IL-17 positive CD4+ T cells from HFD mice and dampens the differentiation of naïve T cells into Th1 cells and Th17 cells. Adiponectin reduces Th17 cell differentiation and restrains glycolysis in an AMPK dependent fashion. Treatment with adult worm extracts of the rodent filarial nematode Litomosoides sigmodontis (LsAg) reduces adipose tissue Th1 and Th17 cell frequencies during HFD and increases adiponectin levels. Stimulation of T cells in the presence of adipocyte-conditioned media (ACM) from LsAg-treated mice reduces Th1 and Th17 frequencies and this effect was abolished when ACM was treated with an adiponectin neutralizing antibody. Collectively, these data reveal a novel role of adiponectin in controlling pro-inflammatory CD4+ T cells during obesity and suggest that the beneficial role of helminth infections and helminth-derived products on obesity and insulin resistance may be in part mediated by adiponectin.