Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a

P I H G Simons,J A P Bons,O Valkenburg,D M De Groot,C G Schalkwijk,T G J Derks,I Telgenkamp,C D A Stehouwer,P Veeraiah,V B Schrauwen-Hinderling,M C G J Brouwers,K M Van Der Waaij

doi:10.1007/s40618-022-01753-2

Abstract

PurposeDe novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels.MethodsA case–control study comparing serum SHBG levels in patients with GSD1a (n = 10) and controls matched for age, sex, and BMI (n = 10). Intrahepatic lipid content and saturated fatty acid fraction were quantified by proton magnetic resonance spectroscopy.ResultsSerum SHBG levels were statistically significantly lower in patients with GSD1a compared to the controls (p = 0.041), while intrahepatic lipid content and intrahepatic saturated fatty acid fraction—a marker of de novo lipogenesis—were significantly higher in patients with GSD1a (p = 0.001 and p = 0.019, respectively). In addition, there was a statistically significant, inverse association of intrahepatic lipid content and saturated fatty acid fraction with serum SHBG levels in patients and controls combined (β: − 0.28, 95% CI: − 0.47;− 0.09 and β: − 0.02, 95% CI: − 0.04;− 0.01, respectively).ConclusionPatients with GSD1a, who are characterized by genetically determined higher rates of de novo lipogenesis, have lower serum SHBG levels than controls.

Highlights

It has long been thought that sex hormone-binding globulin (SHBG) acts only as a simple carrier protein that regulates the bioavailable fraction of testosterone and other sex hormones [1]
The aim of this study was, to examine serum SHBG levels in patients with glycogen storage disease type 1a (GSD1a) and controls matched for age, sex, and BMI, and to study the relationship of intrahepatic lipid (IHL) and saturated fatty acid (SFA) content with serum SHBG
Patients with GSD1a had statistically significantly lower levels of serum insulin compared to controls (p = 0.009) (Fig. 1, panel A), while the IHL content and SFA fraction in patients with GSD1a were statistically significantly higher compared to controls (p = 0.001 and p = 0.019, respectively) (Fig. 1, panel B and C, respectively)

Summary

Introduction

It has long been thought that sex hormone-binding globulin (SHBG) acts only as a simple carrier protein that regulates the bioavailable fraction of testosterone and other sex hormones [1]. SHBG has been identified as a hepatokine that protects from type 2 diabetes [5, 6] These observations stress the need for a better understanding of the regulation of serum SHBG levels in humans. Given the observational nature of that study, we were unable to assess whether the effect of de novo lipogenesis on serum SHBG is causal. This is of importance, since previous in vitro and animal studies have shown that the association between de novo lipogenesis and SHBG appears to be bidirectional, i.e. serum SHBG may directly reduce the rates of de novo lipogenesis [9, 10]

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