Research Progress on the Role and Mechanism of GDF15 in Body Weight Regulation

Abstract

<b><i>Background:</i></b> Growth differentiation factor-15 (GDF15) is a member of the growth differentiation factor subfamily in the transforming growth factor beta superfamily. GDF15 has multiple functions and can regulate biological processes. High levels of GDF15 in the circulation can affect metabolic processes. Studies have shown that GDF15 is associated with changes in body weight. <b><i>Summary:</i></b> This review reviews the current knowledge on the relationship between GDF15 and body weight change, focusing on the role and mechanism of GDF15 in body weight regulation. GDF15 plays an important role in reducing food intake, improving insulin resistance, and breaking down fat, suggesting that GDF15 has an important regulatory effect on body weight. The mechanism by which GDF15 causes reduced food intake may be related to changes in food preference, delayed gastric emptying, and conditioned taste aversion. GDF15 can combat insulin resistance induced by inflammation or protect β cell from apoptosis. GDF15 probably promotes lipolysis through a brain-somatic tissue circuit. Several factors and related signaling pathways are also mentioned that can contribute to the effects of GDF15 on reducing weight. <b><i>Key Message:</i></b> GDF15 plays an important role in weight regulation and provides a new direction for the treatment of obesity. Its effects on resisting obesity are of great significance to inhibiting the progression of metabolic diseases. It is expected to become a new target for regulating body weight, improving obesity, and treating metabolic diseases such as diabetes.

Macrophages as a Source and Target of GDF-15

“…Additionally, they found that the ketogenic diet-induced weight loss was mainly an effect of decreased energy intake, which corroborates previous studies highlighting the anorexigenic role of GDF-15 [105]. A recent review summarizes the relationship between GDF-15 and body weight [106].…”

Nausea, vomiting and conflict in pregnancy

“…Relatively low food intake in early pregnancy, or reduced early pregnancy intake of specific foods, have also been associated with better placental development and reduced fetal loss in other contexts, suggesting mechanistic connections between NVP, which reduces food intake, and benefits to the fetus [ 31 , 41 , 42 ]. Such effects are further supported by the evidence that GDF15 reduces appetite and food intake [ 43 , 44 ], and promotes catabolic activity [ 15 ], including data showing associations of higher serum GDF15 with reduced body weight or body mass index among women [ 45 , 46 ] and mice [ 47 , 48 ].…”

Growth differentiation factor 15 is not modified after weight loss induced by liraglutide in South Asians and Europids with type 2 diabetes mellitus

“…Clinical trials involving individuals with overweight and obesity who were treated with a long‐acting GDF15 receptor analogue showed a reduction in food intake and body weight, supporting the weight‐reducing effect of GDF15 (Benichou et al., 2023 ). Beyond appetite suppression, GDF15 also contributes to weight loss by enhancing energy expenditure, at least in mice (Dong & Xu, 2024 ; Wang et al., 2023 ). Accordingly, metformin also increases energy expenditure in preclinical studies, which was mechanistically at least in part through enhancing activation of energy‐combusting brown adipose tissue (Geerling et al., 2014 ; Ziqubu et al., 2023 ).…”

“…It induces satiety by binding to the glial cell line‐derived neurotrophic factor (GDNF) family receptor α‐like (GFRAL) located in the area postrema and solitary tract of the hindbrain. GFRAL subsequently interacts with the tyrosine kinase co‐receptor RET, which induces phosphorylation of the signalling molecules AKT, extracellular signal‐regulated kinases 1 and 2 (ERK1/2), and phospholipase C, thereby inducing anorexia (Dong & Xu, 2024 ; Emmerson et al., 2017 ; Hsu et al., 2017 ; Ling et al., 2023 ; Mullican et al., 2017 ; Yang et al., 2017 ). In addition, GDF15 induces satiety by signalling through satiety‐inducing cholecystokinin neurons located in the hindbrain (Dong & Xu, 2024 ; Worth et al., 2020 ).…”

“…GFRAL subsequently interacts with the tyrosine kinase co‐receptor RET, which induces phosphorylation of the signalling molecules AKT, extracellular signal‐regulated kinases 1 and 2 (ERK1/2), and phospholipase C, thereby inducing anorexia (Dong & Xu, 2024 ; Emmerson et al., 2017 ; Hsu et al., 2017 ; Ling et al., 2023 ; Mullican et al., 2017 ; Yang et al., 2017 ). In addition, GDF15 induces satiety by signalling through satiety‐inducing cholecystokinin neurons located in the hindbrain (Dong & Xu, 2024 ; Worth et al., 2020 ). Clinical trials involving individuals with overweight and obesity who were treated with a long‐acting GDF15 receptor analogue showed a reduction in food intake and body weight, supporting the weight‐reducing effect of GDF15 (Benichou et al., 2023 ).…”