Abstract
ObjectiveObesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans.DesignA cross‐sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex.ParticipantsHealthy men (n = 34) and women (n = 21) were combined from two cross‐sectional studies. Forty‐two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%).ResultsDNL was inversely associated with SHBG in women (β: −0.015, 95% CI: −0.030; 0.000), but not in men (β: 0.007, 95% CI: −0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin.ConclusionsAn inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.
Highlights
Obesity has become a worldwide health burden that is associated with many health concerns including hypertension, dyslipidaemia, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, gout, osteoarthritis, fractures and gall bladder disease.1–3 Individuals with obesity are commonly characterized by low serum sex hormone binding globulin (SHBG) levels.[4]
The aim of this study was to examine the relationship between de novo lipogenesis (DNL) and serum SHBG in humans
We found an inverse association between DNL, measured with stable isotopes, and serum SHBG in women but not in men
Summary
Obesity has become a worldwide health burden that is associated with many health concerns including hypertension, dyslipidaemia, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, gout, osteoarthritis, fractures and gall bladder disease.1–3 Individuals with obesity are commonly characterized by low serum sex hormone binding globulin (SHBG) levels.[4]. We and others recently showed that a weight reduction programme was associated with an increase in serum SHBG levels.[4,6] the change in intrahepatic lipid (IHL) content was inversely associated with serum SHBG levels.[4]. Excessive accumulation of IHL in obesity can be explained by an increased conversion of glucose to fat (ie de novo lipogenesis [DNL]) and an increased flux of free fatty acids (FFA) from insulin-resistant adipose tissue to the liver.[7] Of interest, previous in vitro studies and mice studies have demonstrated that monosaccharide-induced DNL reduced serum SHBG levels.[8] palmitate—a saturated fatty acid that is the principal end product of DNL—directly reduced SHBG expression in HepG2 cells.[8]. We determined the relationship between DNL, assessed by stable isotopes (the gold standard), and serum SHBG, corrected for potential confounding factors
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