Decreased GPIHBP1 protein levels in visceral adipose tissue partly underlie the hypertriglyceridemic phenotype in insulin resistance

Figures

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  Fig 1. Effect of insulin on GPIHBP1 mRNA and protein expression in HMVEC under static and flow conditions. HMVECs (p4-p5) were cultured with or without 100nM insulin for 24 hours under static (A) or laminar flow conditions (B) as described. Gene expressions of GPIHBP1, LPL, ANGPTL4 and PPARG were analysed in HMVEC under static (Fig 1A) and under flow condition (Fig 1B) were measured. Data are from 4 independent experiments and presented as mean ± SD. Representative immunofluorescence image of HMVECs stained for GPIHBP1 protein under static condition. Differences were analysed using Mann-Whitney nonparametric test. *P<0.05 and **P<0.01.

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  Fig 2. mRNA expression of genes involved in peripheral lipolysis in visceral adipose tissue lysates from Leprdb/m and Leprdb/db mice. Visceral adipose tissue was harvested from Leprdb/m and Leprdb/db mice (n = 8 per group). A. mRNA expression of Gpihbp1, Lpl,Angptl4, Pparg, Irs2 and Akt2. Relative expression was determined using 36B4 as the housekeeping gene.

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  Fig 3. Representative blots for GPIHBP1 protein expression in visceral adipose tissue of Leprdb/m and Leprdb/db mice. Results are expressed as means ± SD; t-test statistics were used to test for differences between the groups. *P<0.05.

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  Fig 4. Detection of monomeric and multimeric forms of Gpihbp1 in visceral adipose lysates from Leprdb/m and Leprdb/db mice. GPIHBP1 protein was separated on SDS-PAGE as described using non-reducing conditions. GPIHBP1 was visualized as described. Data are expressed as mean ± SD. * P<0.05.

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  Fig 5. Correlation between visceral adipose tissue GPIHBP1 protein levels and plasma insulin, plasma glucose, HOMA-IR and BMI. GPIHBP1 protein levels in visceral adipose tissue biopsy specimen were measured in 45 subjects A. correlation with plasma insulin levels, B. plasma glucose levels, C. HOMA-IR and D. BMI. Correlations were tested by Pearson’s correlation coefficient test. BMI, body mass index, HOMA-IR, Homeostasis Assessment of Insulin resistance. HOMA-IR assessed using the formula: glucose [(mmol/L)*insulin (μIU/L)]/22.5.

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  Fig 6. Proposed mechanism. In this illustration we show the proposed underlying mechanism of GPIHBP1 function in TG homeostasis in an insulin resistant state. Hyperinsulinemia leads to decreased protein levels of GPIHBP1 in adipose tissue that results in decreased LPL-mediated peripheral lipolysis of TG. This, in turn, leads to elevated plasma levels of TG and increased VLDL-TG increase due to hepatic insulin resistant state.