Leptin Modulation of Immune Responses and Metabolism
Summary
Leptin, the prototypical adipokine secreted by adipose tissue, operates at the intersection of energy homeostasis and immunity. Beyond its well-known role in appetite suppression and energy expenditure, leptin acts on a broad range of immune cells—macrophages, dendritic cells and T lymphocytes—via the leptin receptor to promote pro-inflammatory programmes. It enhances macrophage phagocytic capacity, skews macrophage polarisation towards the M1 phenotype and stimulates Th1 and Th17 differentiation while constraining regulatory T-cell expansion. Conversely, states of leptin deficiency or resistance, as seen in undernutrition or chronic inflammation, dampen immune vigilance and increase susceptibility to infection. On the metabolic side, leptin influences hepatic lipid metabolism, insulin sensitivity and hypothalamic circuits, forming a feedback loop in which nutrient status calibrates immune readiness. This dual action of leptin underlies its central position in immunometabolism, offering therapeutic avenues for obesity-associated inflammation, autoimmune disorders and metabolic disease.
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Leptin Modulation of Immune Responses and Metabolism publication trend
The graph below shows the total number of articles in leptin modulation of immune responses and metabolism across all publications each year (not limited to Nature Index journals).
Technical terms
Adipokine: A bioactive hormone or cytokine secreted by adipose tissue that influences metabolism and immune function.
Cytokine: A small protein released by cells that modulates communication and responses within the immune system.
T lymphocyte: A type of white blood cell central to adaptive immunity, including helper (CD4+) and cytotoxic (CD8+) subsets.
Immunometabolism: An interdisciplinary field exploring how metabolic processes govern immune cell function and vice versa.
Leptin receptor: A cell-surface protein that binds leptin and initiates intracellular signalling to regulate both metabolic and immune pathways.
References
- Leptin antagonism attenuates hypertension and renal injury in an experimental model of autoimmune disease. Clinical Science (2023).
- Calorie restriction-induced leptin reduction and T-lymphocyte activation in blood and adipose tissue in men with overweight and obesity. International Journal of Obesity (2024).
- Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism*. Journal of Biological Chemistry (2007).
- Role of Leptin in the Activation of Immune Cells. Mediators of Inflammation (2010).
- Changes in Nutritional Status Impact Immune Cell Metabolism and Function. Frontiers in Immunology (2018).
- Obesity, Fat Mass and Immune System: Role for Leptin. Frontiers in Physiology (2018).
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