Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Abstract

Objective Obesity 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. Design A cross‐sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. Participants Healthy 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%). Results DNL 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. Conclusions An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.

The relationships of sex hormone‐binding globulin, total testosterone, androstenedione and free testosterone with metabolic and reproductive features of polycystic ovary syndrome

“…Experimental studies have shown that hepatic de novo lipogenesis, which is increased in obesity and insulin resistance, 26 impairs SHBG synthesis in the liver 27 . We recently demonstrated that de novo lipogenesis, assessed by stable isotopes, is inversely associated with serum SHBG levels in women 28 . Hepatic de novo lipogenesis has also been associated with a disadvantageous lipid profile 29 .…”

“…27 We recently demonstrated that de novo lipogenesis, assessed by stable isotopes, is inversely associated with serum SHBG levels in women. 28 Hepatic de novo lipogenesis has also been associated with a disadvantageous lipid profile. 29 The reduction in the strength of the association between SHBG and serum lipids after adjustment for BMI in the current study is in line with these previous observations and suggests that BMI is an important driver of the metabolic features and low serum SHBG levels that characterize PCOS.…”

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

“…Regression coefficients (β) and 95% confidence intervals (CI) are reported for the associations in the two groups combined. Of note, fasting serum insulin was unavailable in one GSD1a patient, and SFA was only measured in a subset of patients (n = 8) and controls (n = 5) (see "Methods" section) with serum SHBG levels, we could not assess the direction of the association [8]. This is of relevance, since in vitro experiments have also shown that SHBG can affect de novo lipogenesis [9].…”

“…In vitro and animal studies have shown that carbohydrate-induced de novo lipogenesis is one of the mechanisms involved in the downregulation of SHBG levels [7]. We have recently extrapolated these findings to humans, by showing that de novo lipogenesis, measured with stable isotopes, is inversely associated with serum SHBG levels [8]. However, given the observational nature of that study, we were unable to assess whether the effect of de novo lipogenesis on serum SHBG is causal.…”

Overvloed

“…Op die manier kunnen ze naar andere organen vervoerd worden, die het onder andere gebruiken als brandstof. Ten tweede leidt stapeling van vet in de lever ertoe dat er via een stofje -sex hormone binding globulin -ook meer actief testosteron in de bloedbaan terecht komt (Figuur 1) (8,9). Testosteron is het mannelijke hormoon.…”