High glucose stimulating ECM remodeling and an inflammatory phenotype in the IPFP via upregulation of MFAP5 expression.

Extracellular matrix (ECM) remodeling and inflammation in the infrapatellar fat pad (IPFP) are associated with cartilage degeneration and the severity of osteoarthritis (OA). Diabetes is associated with the progression of OA. However, it is still unclear whether diabetes can promote osteoarthritis by targeting the IPFP. In this study, we established a high-fat diet/streptozotocin (HFD/STZ)-induced diabetes mouse model. We found that fibrosis and inflammation were more severe in the IPFP in diabetic mice. Transcriptomic profiling showed that MFAP5 expression was upregulated in IPFPs collected from diabetic mice compared to IPFPs collected from normal mice. We identified that Pdgfrα(+) progenitors were the primary source of MFAP5 in the IPFP under diabetic conditions. In addition, high glucose promoted the expression of MFAP5 in Pdgfrα(+) progenitors by stimulating the translocation of Yap1. Overexpression of MFAP5 in Pdgfrα(+) progenitors promoted fibrogenic differentiation and the production of IL-6. Knocking down the expression of MFAP5 efficiently prevented fibrosis and decreased the level of IL-6 in the IPFP and attenuated cartilage degeneration. Together, these results suggest that MFAP5 may be a potential novel therapeutic target for the treatment of diabetes-induced OA.

Circulating ANGPTL8 Is Associated with the Presence of Metabolic Syndrome and Insulin Resistance in Polycystic Ovary Syndrome Young Women.

BACKGROUND: ANGPTL8 has been reported to be a regulator of lipid metabolism, and it is associated with insulin resistance (IR) and metabolic syndrome (MetS). We investigated whether ANGPTL8 plays a role in MetS. METHODS: ANGPTL8 and adiponectin concentrations were measured in PCOS patients with or without MetS and in their corresponding healthy controls. The association of circulating ANGPTL8 with adiponectin and other parameters was also examined. RESULTS: Circulating ANGPTL8 concentrations were higher in PCOS women with MetS than in those without MetS and in the controls (P < 0.01). ANGPTL8 was positively correlated with age, BMI, FAT%, WHR, SBP, TG, FBG, HbA1c, Fins, and HOMA-IR (all P < 0.01) in the study populations and negatively associated with adiponectin and M-values (P < 0.001). In addition, ANGPTL8 was positively correlated with PRL, LH, TEST, and FAI and negatively correlated with SHBG (all P < 0.01). ROC curve analyses showed that the AUCMetS was 0.87 (P < 0.001), with a sensitivity of 92.4% and specificity of 75.4%, and the AUCIR was 0.82 (P < 0.01), with a sensitivity of 76.4% and specificity of 75.6%. CONCLUSION: ANGPTL8 levels progressively decrease from PCOS patients with MetS to those without MetS and may be a serum marker associated with the degree of metabolic disorders.

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women.