Macrophage Inhibitory Cytokine 1 (MIC-1/GDF15) Decreases Food Intake, Body Weight and Improves Glucose Tolerance in Mice on Normal & Obesogenic Diets

Abstract

Food intake and body weight are controlled by a variety of central and peripheral factors, but the exact mechanisms behind these processes are still not fully understood. Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of obesity. Both under a normal chow diet and an obesogenic diet, the transgenic overexpression of MIC-1/GDF15 in mice leads to decreased body weight and fat mass. This lean phenotype was associated with decreased spontaneous but not fasting-induced food intake, on a background of unaltered energy expenditure and reduced physical activity. Importantly, the overexpression of MIC-1/GDF15 improved glucose tolerance, both under normal and high fat-fed conditions. Altogether, this work shows that the molecule MIC-1/GDF15 might be beneficial for the treatment of obesity as well as perturbations in glucose homeostasis.

Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression

“…In contrast, MIC1 induced anorexia and weight loss in late-stage advanced PCa (Johnen et al 2007). Moreover, overexpression of MIC1 may lead to decreases in food intake, body weight, and adiposity, both under normal and obesogenic dietary conditions (Macia et al 2012). Therefore, the balance between increased caloric intake from an HFD and HFD-associated hyper-production of MIC1 may be important for body weight regulation.…”

Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial

“…Notably, transgenic over-expression of GDF-15 in mice leads to decreased body weight and fat mass and improved glucose tolerance under high fat-fed conditions, suggesting that GDF-15 may serve a compensatory role (33). Studies on GDF-15 deficient mice are required to assess the function of endogenous GDF-15 in this setting.…”

Induction of Growth Differentiation Factor 15 in Skeletal Muscle of Old Taurine Transporter Knockout Mouse

“…Cancer cells produce GDF15, which results in an increase in circulating level of GDF15 in cancer patients. 13) Since overexpression of GDF15 in mice results in a decrease in food intake and a body weight loss, 25) it is assumable that induction of serum GDF15 level may cause anorexia in the patients. Consistently, 18-month-old TauTKO mice but not WT mice display loss of body weight compared to 12-month-old mice.…”