Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor. Although recent studies have suggested that MANF appeared to be associated with insulin resistance, the results have been inconsistent. The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women. We conducted a series of cross-sectional and interventional studies in 90 newly diagnosed patients with PCOS and 60 age- and gender-matched controls. Oral glucose tolerance test and euglycemic-hyperinsulinemic clamps were performed to assess the glucose tolerance and insulin sensitivity. Forty-three women with PCOS were randomly assigned to six months of oral metformin therapy. Serum MANF levels were significantly lower in women with PCOS than in controls. Serum MANF levels were positively correlated with M-value and negatively correlated with body mass index (BMI), body fat percentage (FAT), homeostatic model assessment of insulin resistance (HOMA-IR), and free androgen index (FAI). Multivariate stepwise regression demonstrated that serum MANF levels were independently associated with M-value and FAI. After six months of metformin treatment, there was a significant increase in serum MANF levels in PCOS women. Serum MANF levels are decreased in women with PCOS, and are reversely related to insulin resistance and hyperandrogenism. Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.

Correlation of Significantly Decreased Serum Circulating Mesencephalic Astrocyte-Derived Neurotrophic Factor Level With an Increased Risk of Future Cardiovascular Disease in Adult Patients With Growth Hormone Deficiency

“…However, the expression of MANF is inconsistent in human disease, and studies have shown that circulating serum MANF levels are significantly elevated in patients with primary diabetes and early diabetes with abnormal glucose tolerance (22). In another PCOS-related study, it was noted that the circulating serum MANF level of the PCOS population was significantly lower than that of the control group (23). In our study, a trend toward significantly lower circulating MANF levels was found in the AGHD population.…”

MANF: an emerging therapeutic target for metabolic diseases

“…Effect of MANF on glucose homeostasis Impaired glucose homeostasis is often caused by decreased insulin sensitivity in multiple tissues and/or insufficient insulin secretion in dysfunctional pancreatic β cells. We and others found a correlation between circulating MANF level and insulin resistance in patients with prediabetes and T2DM [17,37] (Table 1). In addition to clinical observations, the role of MANF in modulating insulin sensitivity has been studied in various mouse models.…”

Increased serum concentrations of Mesencephalic astrocyte-derived neurotrophic factor in patients and rats with ischemic stroke

“…This finding is consistent with other studies showing that decreased serum MANF resulted in the decline of alleviating ER stress. 23,31 Our data suggest that early detection of MANF following TIA have a potential role in improving the immediate risk stratification of patients. This in turn may lead to the development of new pharmacological treatment and more aggressive Table 1.…”