Adipose tissue expression of CCL19 chemokine is positively associated with insulin resistance

Introduction. Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques.Methods. RBP4 serum levels were evaluated in HD (n=16) and matched healthy controls (C;n=16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n=7) and in hemodialysis patients (n=10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF).Results. HOMA index (P<0.05) and serum RBP4 (P<0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P<0.05). RBP4 mRNA was lower in HD compared to C (P<0.05) and positively correlated with kidney function (P<0.05) and GLUT4 mRNA (P<0.001). Transplant or HDF reduced circulating RBP4 (P<0.01andP<0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels.

Download Full-text

Increased adipose tissue expression of Grb14 in several models of insulin resistance

The FASEB Journal ◽

10.1096/fj.03-0824fje ◽

2004 ◽

Vol 18 (9) ◽

pp. 965-967 ◽

Cited By ~ 43

Author(s):

Bertrand Cariou ◽

Nadège Capitaine ◽

Véronique Le Marcis ◽

Nathalie Vega ◽

Véronique Béréziat ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Tissue Expression

Download Full-text

Elevated adipose tissue expression of IRAK-1 is linked with inflammatory state in obesity and insulin resistance

10.26226/morressier.59d51842d462b80296ca36ad ◽

2017 ◽

Author(s):

Kochumon Shihab

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Tissue Expression ◽

Inflammatory State

Download Full-text

Increased adipose tissue expression of IL-18R and its ligand IL-18 associates with inflammation and insulin resistance in obesity

Immunity Inflammation and Disease ◽

10.1002/iid3.170 ◽

2017 ◽

Vol 5 (3) ◽

pp. 318-335 ◽

Cited By ~ 20

Author(s):

Rasheed Ahmad ◽

Reeby Thomas ◽

Shihab Kochumon ◽

Sardar Sindhu

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Tissue Expression

Download Full-text

Improvement of Insulin Sensitivity after Peroxisome Proliferator-Activated Receptor-α Agonist Treatment Is Accompanied by Paradoxical Increase of Circulating Resistin Levels

Endocrinology ◽

10.1210/en.2005-1624 ◽

2006 ◽

Vol 147 (9) ◽

pp. 4517-4524 ◽

Cited By ~ 45

Author(s):

M. M. Haluzik ◽

Z. Lacinova ◽

M. Dolinkova ◽

D. Haluzikova ◽

D. Housa ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Mrna Expression ◽

Liver Steatosis ◽

Tissue Expression ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Insulin Levels ◽

Fenofibrate Treatment ◽

Adiponectin Mrna

We studied the effect of peroxisome proliferator-activated receptor-α (PPAR-α) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-α agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-α activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.

Download Full-text

4261 Insulin Sensitizing Effects of Vitamin D Mediated through Reduced Adipose Tissue Inflammation and Fibrosis: Evidence from a Human Randomized Trial and Mice Studies

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.304 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 97-98

Author(s):

Eric Lontchi Yimagou ◽

Sona Kang ◽

Kehao Zhang ◽

Akankasha Goyal ◽

Jee Young You ◽

...

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Adipose Tissue ◽

Tissue Expression ◽

Hepatic Insulin Resistance ◽

Adipose Tissue Inflammation ◽

Collagen Vi ◽

Tissue Inflammation ◽

Tnf Α ◽

Tgf Β1

OBJECTIVES/GOALS: Vitamin D [25(OH)D], known to have anti-inflammatory and anti-fibrotic effects in other tissues, may also impact adipose tissue. We designed parallel studies in humans and rodents to define the effects of vitamin D on adipose tissue inflammation and fibrosis, and on systemic insulin resistance. METHODS/STUDY POPULATION: We performed a randomized, double-blinded placebo-controlled trial to examine the effects of repleting vitamin D at to two levels (to >30 ng/ml and to > 50 ng/ml) in 25(OH)D-deficient (<20 ng/ml), insulin resistant, overweight-to-obese humans (n = 19). A comprehensive study of whole-body insulin action was undertaken with euglycemic stepped hyperinsulinemic clamp studies, both before (1st visit) and after administration of vitamin D or placebo (2nd visit and 3rd visit). Adipose tissue fibrosis and inflammation were quantified by ‘real-time’ rt-PCR and immunofluorescence. To determine whether vitamin D’s effects are mediated through adipocytes, we performed hyperinsulinemic clamp studies and adipose tissue analysis in an adipocyte-specific vitamin D receptor knockout (VDR KO) mouse model. RESULTS/ANTICIPATED RESULTS: 25(OH)D repletion (to >30 ng/ml) was associated with reductions in adipose tissue expression of inflammatory (0.6-0.7-fold decreased expression of TNF-α, IL-6, iNOS and PAI-1) and pro-fibrotic (0.4-0.8-fold decreased expression of TGF-β1, HiF1α, Collagen I, V, VI and MMP7) factors, decreased collagen VI immunofluorescence (p = 0.02) and improved hepatic insulin sensitivity in humans, with suppression of endogenous glucose production (EGP) (1.28 ± 0.20 vs 0.88 ± 0.18 mg/kg/min, p = 0.03). Compared to wild type (WT), VDR KO mice exhibited increased adipose tissue expression of several pro-inflammatory (Tnf-α, iNos, Pai-1, Mcp-1 and F4/80; 4-10 fold) and pro-fibrotic genes (Tgf-β1, Collagen VI, and Tsp1; 2-4 fold), in concert with hepatic insulin resistance (EGP 10 ± 3 vs 3 ± 2 mg/kg/min in WT, p = 0.021). DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these complementary human and rodent studies establish a beneficial role of vitamin D to improve hepatic insulin resistance, likely by restraining adipose tissue inflammation and fibrosis. Thus, normalizing 25(OH)D levels could have metabolic benefits in targeted individuals. CONFLICT OF INTEREST DESCRIPTION: N/A

Download Full-text