Relevance of low testosterone to nonalcoholic fatty liver disease

Mody, Avni; White, Donna L.; Kanwal, Fasiha; García, José Manuel Pérez

doi:10.1097/xce.0000000000000057

Cited by 55 publications

(41 citation statements)

References 65 publications

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“…HFD intake decreased serum and intra‐testicular FSH, LH, testosterone and estradiol levels, which are consistent with previous reports 41,65 . The significant down‐regulation of AR and LHR transcript levels in the testis in HFD group relative to NC group may have compounded the already decreased intra‐testicular FSH, LH, testosterone and estradiol levels in HFD group.…”

Section: Discussionsupporting

confidence: 91%

Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes

et al. 2020

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Background Steroidogenesis decline is reported to be one of the mechanisms associated with obesity‐induced male factor subfertility/infertility. Objectives We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity‐induced steroidogenesis and spermatogenesis decline. Materials and methods Twenty‐four adult male Sprague Dawley rats weighing 250‐300 g were randomized into four groups (n = 6/group), namely; normal control, high‐fat diet, high‐fat diet plus orlistat preventive group and high‐fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high‐fat diet for 12 weeks (high‐fat diet plus orlistat preventive group) or administered from week 7‐12 post‐ high‐fat diet feeding (high‐fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses. Results Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra‐testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase were significantly decreased in the testes of the high‐fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high‐fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high‐fat diet‐induced obese male rats, with the preventive group (high‐fat diet plus orlistat preventive group) having better results relative to the treatment group (high‐fat diet plus orlistat treatment group). Discussion and Conclusion Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up‐regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.

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Section: Discussionsupporting

confidence: 91%

Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes

et al. 2020

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“…By contrast, the female component genes showed no significant enrichment after correction for multiple hypothesis testing (Benjamini-Hochberg corrected p > 0.1). In men, low serum testosterone levels are associated with cirrhosis and non-alcoholic fatty liver disease (NAFLD), with decreasing levels corresponding to increased disease severity(Sinclair et al 2015;Mody et al 2015;Yim et al 2018) . Previous studies also find this inverse relationship in post-menopausal women(Sinclair et al 2015;Mody et al 2015;Yim et al 2018) ; however,…”

mentioning

confidence: 99%

Sex-specific genetic effects across biomarkers

Flynn

Tanigawa

Rodríguez

et al. 2019

Preprint

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Sex differences have been shown in laboratory biomarkers; however, the extent to which this is due to genetics is unknown. In this study, we infer sex-specific genetic parameters (heritability and genetic correlation) across 33 quantitative biomarker traits in 181,064 females and 156,135 males from the UK Biobank study. We apply a Bayesian mixture model, Sex Effects Mixture Model, to Genome-wide Association Study summary statistics in order to (1) estimate the contributions of sex to the genetic variance of these biomarkers and (2) identify variants whose statistical association with these traits is sex-specific. We find that the genetics of most biomarker traits are shared between males and females, with the notable exception of testosterone, where we identify 119 female and 444 male-specific variants. These include protein-altering variants in steroid hormone production genes ( POR, CYP3A43, UGT2B7 ). Using the sex-specific variants as genetic instruments for Mendelian Randomization, we find evidence for causal links between testosterone levels and height, body mass index, waist circumference, and type 2 diabetes. We also show that sex-specific polygenic risk score models for testosterone outperform a combined model. Overall, these results demonstrate that while sex has a limited role in the genetics of most biomarker traits, sex plays an important role in testosterone genetics.

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“…For example, reduced testosterone levels in men were associated with an increased risk of NAFLD [32] , whereas in women, elevated circulating testosterone levels increased the prevalence of NAFLD [33] . In addition, testosterone de ciency increases visceral fat content and insulin resistance in men; while in women, high androgen levels increase insulin resistance and visceral fat [34] . As a classical agent with sex-disparity effects, pioglitazone has been reported to both decrease testosterone levels in men with diabetes [35] , and in women with polycystic ovary syndrome (PCOS) [36] .…”

Section: Discussionmentioning

confidence: 99%

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism

Wang

Chang

et al. 2020

Preprint

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Background: Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism.Methods: This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT)* with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n= 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15mg qd, and LSI + berberine (BBR) 0.5g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H- MRS) to assess liver fat content. Results: As compared with LSI, PGZ + LSI treatment induced further decreased liver fat content in women (-15.24% ± 14.54% vs. -8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (-9.95% ± 15.18% vs. -12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism.Conclusion: The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism.* Trial registration: Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282. Registered 3 March 2008, https://register.clinicaltrials.gov.

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Relevance of low testosterone to nonalcoholic fatty liver disease

Cited by 55 publications

References 65 publications

Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes

Orlistat attenuates obesity‐induced decline in steroidogenesis and spermatogenesis by up‐regulating steroidogenic genes

Sex-specific genetic effects across biomarkers

Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism

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