Subjects with obesity frequently have elevated serum vasopressin levels, noted by measuring the stable analog, copeptin. Vasopressin acts primarily to reabsorb water via urinary concentration. However, fat is also a source of metabolic water, raising the possibility that vasopressin might have a role in fat accumulation. Fructose has also been reported to stimulate vasopressin. Here, we tested the hypothesis that fructose-induced metabolic syndrome is mediated by vasopressin. Orally administered fructose, glucose, or high-fructose corn syrup increased vasopressin (copeptin) concentrations and was mediated by fructokinase, an enzyme specific for fructose metabolism. Suppressing vasopressin with hydration both prevented and ameliorated fructose-induced metabolic syndrome. The vasopressin effects were mediated by the vasopressin 1b receptor (V1bR), as V1bR-KO mice were completely protected, whereas V1a-KO mice paradoxically showed worse metabolic syndrome. The mechanism is likely mediated in part by de novo expression of V1bR in the liver that amplifies fructokinase expression in response to fructose. Thus, our studies document a role for vasopressin in water conservation via the accumulation of fat as a source of metabolic water. Clinically, they also suggest that increased water intake may be a beneficial way to both prevent or treat metabolic syndrome.

Metabolic dysfunction-associated steatotic liver disease (MASLD) [previously termed nonalcoholic fatty liver disease (NAFLD)] is estimated to be the most common chronic liver disease worldwide, affecting 25% of the world’s population and becoming the leading cause of liver transplant in the US. The progression of MASLD from simple hepatic steatosis to the more severe metabolic dysfunction-associated steatohepatitis (MASH) [previously nonalcoholic steatohepatitis (NASH)] has critically important impacts on clinical outcomes. Early detection and staging of disease severity, along with lifestyle modifications and treatment of comorbid conditions, is the best way to prevent the progression or reverse the course of the disease. Although noninvasive imaging and predictive indices are available for the evaluation of hepatic fibrosis, the only way to diagnose MASH remains liver biopsy despite the risk for complications and being less desired by patients. Hence, there is a need to develop noninvasive tests to aid in both the diagnosis and monitoring of MASH, especially with the recent emergence of liver-directed therapy for “at risk” MASH (MASH with NAS ≥ 4 and Stage ≥ F2 Fibrosis). The goal of the current review is to cover the most recent pathophysiology, current diagnostic methods, and recent advances to aid in the diagnosis of MASH.

Background/Objectives: Quantitative urine monitors are increasingly being used for a personalized approach to improve menstrual cycle knowledge and to manage fertility. Although several studies have evaluated urine fertility monitors in regular cycles, there is limited research in the use of quantitative monitors in reproductive disorders, such as polycystic ovarian syndrome (PCOS). Methods: Urine hormone data was collected with the Mira monitor from 20 participants, 10 of whom had PCOS and a matched group who had regular cycles. The main aim of this study was to evaluate the levels of luteinizing hormone (LH), estrone-3-glucuronide (E₁3G), and pregnanediol glucuronide (PDG) in PCOS menstrual cycles compared to regular cycles. Results: Women with PCOS had higher BMI than regular cycling women (p=0.02). PCOS cycles were longer (p<0.05), peak day was later in the menstrual cycle (p<0.001), and luteal length was shorter (p < 0.01) compared to regular cycles. In whole cycle comparisons, E₁3G was found to be lower in PCOS cycles (p<0.01) and PDG was found to be higher in PCOS cycles (p<0.05). E₁3G was also lower in the follicular phase of and late luteal phase of PCOS cycles (p<0.00001). Conclusions: The results of this study demonstrate the feasibility of detecting hormonal differences in PCOS compared to regular cycles with at-home measurements with the Mira monitor. The metabolic dysregulation of PCOS is a possible factor in these hormone changes. Larger studies with different sub-types of PCOS will be needed to further clarify these changes and to understand the pathophysiology behind these hormonal changes.