ArticleThe Journal of clinical investigation2007
Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.Clinical chemistry · 2023Pooled it
- Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update.Archives of gynecology and obstetrics · 2021Pooled it
- A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.PLoS genetics · 2012Pooled it
- Metabolic benefits of ketohexokinase inhibition in individuals with MASLD: a randomized placebo-controlled crossover trial.Nature metabolism · 2026Trial
- Circulating sex hormone binding globulin levels are modified with intensive lifestyle intervention, but their changes did not independently predict diabetes risk in the Diabetes Prevention Program.BMJ open diabetes research & care · 2020Trial
- Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome.Journal of endocrinological investigation · 2013Trial
- Resistance training increases SHBG in overweight/obese, young men.Metabolism: clinical and experimental · 2013Trial
- Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome.Fertility and sterility · 2009Trial
- Neuroendocrine regulation of adipose partitioning in polyendocrine metabolic ovarian syndrome: the gut-brain-adipose axis.Journal of endocrinological investigation · 2026Review
- Beneficial Hepatokines in MASLD/MASH: Therapeutic Potentials and Drug Delivery Challenges.International journal of molecular sciences · 2026Review
- FGF21 and SHBG as Putative Hepatic Axes in Maternal Metabolic Adaptation: A Hypothetical Framework for Postpartum Insulin Sensitivity Restoration.Biomolecules · 2026Review
- Nutrition Across the Life Course and Risk of Young-Onset Breast Cancer: Mechanisms, Evidence, and Prevention Opportunities.Nutrients · 2026Review
- Sex hormone-binding globulin and coronary heart disease: a narrative review of associations and biomarker potential.Journal of thoracic disease · 2026Review
- Sex Hormone-Binding Globulin Prevents Carbon Tetrachloride-Induced Liver Fibrosis Development.International journal of molecular sciences · 2026Article
- EDL6D, a bioactive peptide phenocopying SHBG-associated metabolic effects: a new preclinical lead compound for treating the metabolic dysfunction-associated fatty liver disease.Journal of translational medicine · 2026Article
- Sex steroids, SHBG and type 2 diabetes in women: what do we really know?Diabetologia · 2026Review
- Tongue color tones in Traditional Chinese Medicine correlate with liver histology of metabolic dysfunction-associated steatohepatitis in morbidly obese patients undergoing metabolic and bariatric surgery.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Sex-specific associations of SHBG, testosterone, and obesity with cholecystectomy risk: a population-based cohort study.Biology of sex differences · 2026Article
- On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2025Review
- SHBG, Testosterone, and Type 2 Diabetes Risk in Middle-Aged African Women: Exploring the Effect of HIV and Menopause.The Journal of clinical endocrinology and metabolism · 2025Observational
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver produces plasma sex hormone-binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. In overweight children and adults, low plasma SHBG levels are a biomarker of the metabolic syndrome and its associated pathologies. Here, we showed in transgenic mice and HepG2 hepatoblastoma cells that monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes. This occurred via a downregulation of hepatocyte nuclear factor-4alpha (HNF-4alpha) and replacement of HNF-4alpha by the chicken OVA upstream promoter-transcription factor 1 at a cis-element within the human SHBG promoter, coincident with repression of its transcriptional activity. The dose-dependent reduction of HNF-4alpha levels in HepG2 cells after treatment with glucose or fructose occurred in concert with parallel increases in cellular palmitate levels and could be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition of lipogenesis prevented monosaccharide-induced downregulation of HNF-4alpha and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4alpha levels, which in turn attenuated SHBG expression. This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.