NPC1 in human white adipose tissue and obesity.

Clara Bambace,Agné Kulyté,Peter Arner,Ingrid Dahlman

doi:10.1186/1472-6823-13-5

Abstract

BackgroundGenetic studies have implicated the NPC1 gene (Niemann Pick type C1) in susceptibility to obesity.MethodsTo assess the potential function of NPC1 in obesity, we determined its expression in abdominal white adipose tissue (WAT) in relation to obesity. NPC1 mRNA was measured by RT-qPCR in lean and obese individuals, paired samples of subcutaneous (sc) and omental (om) WAT, before and after weight loss, in isolated adipocytes and intact adipose pieces, and in primary adipocyte cultures during adipocyte differentiation. NPC1 protein was examined in isolated adipocytes.ResultsNPC1 mRNA was significantly increased in obese individuals in scWAT and omWAT and downregulated by weight loss. NPC1 mRNA was enriched in isolated fat cells of WAT, in scWAT versus omWAT but not modified during adipocyte differentiation. NPC1 protein mirrored expression of mRNA in lean and obese individuals.ConclusionsNPC1 is highly expressed in human WAT adipocytes with increased levels in obese. These results suggest that NPC1 may play a role in adipocyte processes underlying obesity.

Highlights

Genetic studies have implicated the Niemann-Pick C1 gene (NPC1) gene (Niemann Pick type C1) in susceptibility to obesity
NPC1 mRNA expression was increased in omWAT (P=0.013, Cohort 2, Figure 1B) of obese females
NPC1 mRNA levels were normalized by weight loss following either bariatric surgery or behavioral modification (P=0.0452, Cohort 3, Figure 1C)

Summary

Introduction

Genetic studies have implicated the NPC1 gene (Niemann Pick type C1) in susceptibility to obesity. Obesity is characterized by an excess of white adipose tissue (WAT) and marked adipocyte dysfunction that increase the risk for insulin resistance, type 2 diabetes mellitus and cardiovascular disease. A recent genome-wide association study report has indicated that the Niemann-Pick C1 gene (NPC1) is associated with early-onset and morbid adult obesity [1]. A recent report showed that NPC1+/− male mice, when fed a high fat diet, deposited more fat and were heavier than their wild-type siblings in the absence of hyperphagia. They developed adipocyte hypertrophy [5,6].

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Results

Conclusion