Growth Differentiation Factor 15 in Cardiovascular and Metabolic Disorders
Summary
Growth Differentiation Factor 15 (GDF15) is a stress‐responsive cytokine belonging to the Transforming Growth Factor‐β superfamily. Expressed at low levels in healthy tissues, its synthesis markedly increases in response to cellular injury, inflammation and metabolic perturbation. Circulating GDF15 signals via the hindbrain‐restricted receptor GFRAL to regulate appetite, energy expenditure and aversive feeding. In cardiovascular contexts, elevated GDF15 serves as a robust biomarker for heart failure, atherosclerosis and endothelial dysfunction, and may exert cardioprotective effects by modulating inflammatory and apoptotic pathways. Metabolically, GDF15 influences insulin sensitivity, adipose tissue function and lipid handling, offering prospects for therapeutic intervention in obesity, type 2 diabetes and non‐alcoholic fatty liver disease. The dual roles of GDF15 as a disease indicator and a physiological regulator underscore its global significance and translational potential in managing cardiometabolic disorders.
Research from Nature Portfolio
Recent studies have elucidated how GDF15 enhances weight loss by preserving skeletal muscle energy expenditure during caloric restriction. This action involves GFRAL–β‐adrenergic signalling that promotes fatty acid oxidation and calcium futile cycling, resulting in greater reductions in non-alcoholic fatty liver disease and improved glycaemic control compared with diet alone. Parallel research has demonstrated that macrophage‐derived GDF15 supports oxidative function and anti-inflammatory (M2-like) polarisation in adipose tissue. Restoration of GDF15 levels in insulin-resistant mouse models reverses adipose inflammation and systemic glucose intolerance, highlighting a cell-autonomous mechanism by which GDF15 mitigates metabolic dysfunction.
Growth Differentiation Factor 15 in Cardiovascular and Metabolic Disorders publication trend
The graph below shows the total number of articles in growth differentiation factor 15 in cardiovascular and metabolic disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Growth Differentiation Factor 15 (GDF15): A stress‐induced cytokine of the TGF‐β family that circulates in response to tissue injury and metabolic stress.
GFRAL: A receptor expressed in the hindbrain that mediates GDF15’s effects on appetite and energy balance.
Adaptive Thermogenesis: The reduction in energy expenditure that normally accompanies caloric restriction.
Macrophage Polarisation: The process by which macrophages adopt pro-inflammatory (M1) or anti-inflammatory (M2) functional phenotypes.
Non-alcoholic Fatty Liver Disease (NAFLD): A condition characterised by the accumulation of fat in the liver unrelated to excessive alcohol intake.
Cachexia: A syndrome of involuntary weight loss and muscle wasting associated with chronic illness.
Conditioned Taste Aversion: A learned avoidance of a flavour after it has been associated with an adverse physiological response.
References
- GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature (2023).
- GDF‐15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. Journal of Diabetes Research (2015).
- GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans. Cell Metabolism (2019).
- GDF15: A Hormone Conveying Somatic Distress to the Brain. Endocrine Reviews (2020).
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