Adipose Thermogenesis and Crosstalk: Signaling Networks in Obesity, Metabolic Disease and Beyond

Dear Colleagues,

Adipose tissue is a dynamic endocrine and thermogenic organ that shapes whole-body glucose homeostasis and energy balance. White adipose tissue (WAT) stores energy, whereas brown adipose tissue (BAT) and inducible beige adipocytes dissipate energy via non-shivering thermogenesis. In adult humans, both classical BAT and recruitable beige fat exist, and their activity associates inversely with adiposity and age, spotlighting adipose thermogenesis as a therapeutic avenue for obesity and related cardiometabolic diseases. Yet thermogenesis must be precisely tuned; excess or misplaced activation contributes to energy-wasting states (e.g., cancer cachexia, severe burns, infection, and hyperthyroidism). Despite rapid progress, the field still lacks a comprehensive map of the signaling nodes and inter-organ circuits that drive, or brake, thermogenic programs.

Aim and Scope

This Special Issue aims to gather research on mechanistic and translational advances that illuminate signaling crosstalk controlling adipose thermogenesis, white-fat browning, and adipose-driven metabolic disease. We welcome studies spanning molecular pathways, cellular ecosystems, inter-organ axes, and therapeutic strategies, including work that reconciles species differences and bridges preclinical models with human physiology.

Topics of Interest include, but are not limited to, the following:

(1) Thermogenic signaling pathways: β-adrenergic/GPCR/cAMP/PKA, thyroid hormone, natriuretic peptides, FGF/FGFR (e.g., FGF21), BMP/SMAD, insulin/IGF/PI3K/AKT/mTOR, AMPK, HIF/hypoxia, bile acid/TGR5, purinergic signaling.

(2) UCP1-dependent and UCP1-independent thermogenesis: creatine and Ca²⁺ futile cycles, lipid cycling, mitochondrial uncoupling, peroxisomal and ER contributions.

(3) WAT browning and beige plasticity: depot specificity, developmental origins, transcriptional/epigenetic control, ECM remodeling, angiogenesis, innervation.

(4) Adipose secretome and crosstalk: adipokines/batokines and their actions on liver, muscle, pancreas, brain, gut, and heart; endocrine, paracrine, and neuroimmune circuits.

(5) Immunometabolic regulation: macrophages, ILC2/eosinophils, T/B cells, cytokine networks shaping thermogenic tone.

(6) Physiology and pathophysiology: obesity, insulin resistance/T2D, hypertension, CVD, MASLD/NAFLD, cold exposure/acclimation, exercise; states requiring restraint of thermogenesis (cachexia, burns, infection, hyperthyroidism, under-nutrition).

(7) Human relevance and translation: PET-CT and other imaging of BAT, human depot heterogeneity, age/sex differences, environmental exposures, pharmacotherapy (e.g., GLP-1/GIP agonists, β3-agonists, TH analogs, TGR5 agonists).

(8) Methodological advances: single-cell and spatial omics, lineage tracing, CRISPR screens, quantitative proteomics/lipidomics/metabolomics, in vivo thermogenic phenotyping, computational modeling/AI for pathway discovery.

(9) Therapeutic targets: identification/validation of druggable nodes (ligands, receptors, kinases, transcription factors, epigenetic regulators), delivery strategies, safety/efficacy and tissue selectivity.

Article Types

Original research articles (mechanistic, integrative physiology, translational or clinical); reviews and mini-reviews (state-of-the-art syntheses, controversies, future directions); perspectives/opinions (hypothesis-driven viewpoints, roadmaps for the field); methods/resource reports (novel assays, datasets, models, or analytical pipelines)

Call for Papers

Adipose Thermogenesis and Crosstalk: We welcome mechanistic and translational studies that decode how signaling networks and inter-organ circuits govern adipose thermogenesis, WAT browning, and systemic metabolism. From UCP1-denpendent or independent heat production and the adipose secretome to neuroimmune regulation and human BAT imaging, we seek targets and frameworks that can be converted into safe, effective therapies for obesity and cardiometabolic disease, while clarifying when, where, and how thermogenesis should be restrained in wasting conditions. Original research, reviews/mini-reviews, perspectives, and methods/resources are welcome.

Dr. Lei Huang
Guest Editor

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