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

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2417

Special Issue Editor

Dr. Lei Huang

E-Mail Website
Guest Editor
Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Interests: epigenetic and transcriptional regulation of brown fat (BAT) development; inguinal white adipose tissue (iWAT) browning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adipose thermogenesis
  • BAT
  • WAT browning
  • adipokines
  • batokines
  • UCP1
  • single-cell/spatial omics
  • metabolic disease
  • obesity
  • insulin resistance
  • cardiovascular risk

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Published Papers (3 papers)

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Research

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22 pages, 13973 KB  
Article
Smilax china L. Extract Alleviates Metabolic-Associated Fatty Liver Disease by Regulating Gut Microbiota and Bile Acid Metabolism
by Shiyuan Cheng, Huijun Li, Zhiying Sun, Yue Xiong, Jing Li, Jiaying Tian, Yue Shen, Li Shen, Jingyu Yang, Yuying Yang, Dan Liu, Qiong Wei, Chao Huang and Xiaochuan Ye
Metabolites 2026, 16(1), 31; https://doi.org/10.3390/metabo16010031 - 26 Dec 2025
Viewed by 1175
Abstract
Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax [...] Read more.
Background: Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. Smilax china L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of Smilax china L. extract (SCE) on MAFLD and to elucidate the pharmacological mechanisms. Methods: A rat model of MAFLD was induced through a high-fat diet (HFD), and the model rats subsequently received SCE as a therapeutic intervention for six weeks. The analysis involved 16S rDNA sequencing, untargeted fecal metabolomics, and targeted bile acid metabolomics to investigate the effects of SCE on the gut microbiota and bile acid metabolism. Results: Hepatic steatosis and lipid accumulation were significantly alleviated by the SCE treatment. SCE treatment modulated the gut microbiota disorder, by enhancing the relative abundance of the beneficial gut microbiota, including Clostridium, Oscillospira, and Romboutsia. Untargeted fecal metabolomics revealed a significant enrichment of the metabolites in secondary bile acid biosynthesis. Targeted bile acid metabolomics revealed that SCE reversed the abnormal fecal bile acid metabolic profile, such as HDCA, LCA, and T-β-MCA. These changes activated FXR and PPARα receptors to improve the lipid metabolism by regulating bile acid synthesis. Conclusions: Our study provides evidence that SCE alleviates MAFLD through regulation of the gut microbiota, bile acid metabolism, and activation of the FXR/PPARα pathway, illustrating the mechanism of action of SCE in MAFLD from a novel perspective, and further highlights its therapeutic potential. Full article
(This article belongs to the Special Issue Adipose Thermogenesis and Crosstalk: Signaling Networks in Obesity, Metabolic Disease and Beyond)
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Review

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38 pages, 1863 KB  
Review
TCM-Derived Natural Compounds Targeting the Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease: Gut–Liver Axis Mechanisms, Safety Considerations, and Translational Challenges
by Huailin Deng and Ruiqiu Zhang
Metabolites 2026, 16(5), 342; https://doi.org/10.3390/metabo16050342 - 19 May 2026
Abstract
The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising [...] Read more.
The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising application prospects in the prevention and treatment of MASLD. However, basic research on their toxicity still lags behind, and issues related to safety and clinical translation urgently need attention. This article systematically reviews the research progress on how flavonoids, triterpenoids, alkaloids, and polysaccharides improve hepatic steatosis, inflammatory responses, and metabolic disorders from a toxicological perspective by reshaping the intestinal microbiota, repairing the intestinal mucosal barrier, regulating short-chain fatty acid and bile acid metabolism, and synergistically acting on signaling pathways such as TLR4/NF-kB, FXR, TGR5, SIRT1, and the NLRP3 inflammasome. Furthermore, by combining methods such as 16S rRNA sequencing, metagenomics, metabolomics, and multi-omics integration, the article analyzes their application value and limitations in toxicological mechanism research, and discusses the translational bottlenecks faced by Chinese herbal monomers in pharmacokinetics, bioavailability, quality standardization, targeted delivery, and toxicological safety. Existing evidence indicates that Chinese herbal monomers have a three-in-one intervention advantage of microecological remodeling-metabolic regulation-inflammation inhibition, but their long-term medication safety, toxic target organs, dose-effect/toxicity relationships, and potential drug interactions still need further clarification. This article aims to provide a systematic reference for the safety evaluation and clinical translational research of Chinese herbal monomers in the prevention and treatment of MASLD. Full article
(This article belongs to the Special Issue Adipose Thermogenesis and Crosstalk: Signaling Networks in Obesity, Metabolic Disease and Beyond)
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Other

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18 pages, 1890 KB  
Systematic Review
The Effects of High-Intensity Interval Training on Inflammatory Cytokines in Children and Adolescents with Obesity: A Systematic Review and Meta-Analysis
by Meng Cao, Pei Sun, Xiaodong Wang and Mengxian Zhao
Metabolites 2026, 16(1), 88; https://doi.org/10.3390/metabo16010088 - 21 Jan 2026
Viewed by 889
Abstract
Background: High-intensity interval training (HIT) is a time-efficient strategy to improve metabolic health in children, but its impact on inflammatory markers is still unclear. Therefore, we conducted a meta-analysis to examine the role of HIT on pro-inflammatory cytokines including C-reactive protein (CRP), [...] Read more.
Background: High-intensity interval training (HIT) is a time-efficient strategy to improve metabolic health in children, but its impact on inflammatory markers is still unclear. Therefore, we conducted a meta-analysis to examine the role of HIT on pro-inflammatory cytokines including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in children with overweight/obesity. Methods: A meta-analysis was conducted following PRISMA guidelines. PubMed, Web of Science, Scopus, and Embase were searched up to 31 July 2025, for studies involving children with overweight/obesity aged 6 to 18 years. Randomized controlled trials and non-randomized controlled trials with outcome measurements that included CRP, IL-6, and TNF-α were included. Random-effects models were used to aggregate a mean effect size (ES) with 95% confidence intervals (CI), and potential moderators were explored. Results: In total, 768 participants from 15 studies were included. HIT significantly improved CRP (574 participants, 13 studies, SMD = −0.63, 95% CI: −1.02 to −0.24, p < 0.01) when compared to control group/pre-intervention. There were no significant effects on IL-6 and TNF-α, and no differences when compared to moderate-intensity training. Subgroup analyses indicated greater effectiveness in intervention duration, work-and-rest ratio, and work time were the significant moderators (p < 0.05). Conclusions: High-intensity interval training is effective for reducing CRP levels in children with obesity. Intervention duration, work-and-rest ratio, and work time can affect the intervention effects of HIT. Full article
(This article belongs to the Special Issue Adipose Thermogenesis and Crosstalk: Signaling Networks in Obesity, Metabolic Disease and Beyond)
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