What is the clinical evidence from this study?

Study design: Other. Population: Obesity. Intervention: High-fat diet vs. Normal diet (10% kcal from fat). Primary outcome: Adipogenesis and inflammatory marker expression in co-cultured adipose tissue immune cells and adipocytes.

June 3, 2025Frontiers in Immunology21 citationsOpen Access

High-fat diet-induced adipose tissue-resident macrophages, T cells, and dendritic cells modulate chronic inflammation and adipogenesis during obesity

Q: What does this research mean for the field?

Adipose tissue-resident macrophages, T cells, and dendritic cells from high-fat diet-fed mice coordinate to stimulate adipocyte differentiation and sustain chronic inflammation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

MMMousumi MandalUniversity of Tennessee Health Science Center MMMd Abdullah Al MamunUniversity of Tennessee Health Science Center ARAhmed RakibUniversity of Tennessee Health Science Center

Key Result

Macrophages, T cells, and dendritic cells from high-fat diet-fed mice coordinated to stimulate adipocyte differentiation and sustain chronic inflammation in adipose tissue.

Structured PICO

Population

Wild-type C57BL/6 male mice fed a high-fat diet or normal diet for 12 weeks to study adipose tissue inflammation and immune cell crosstalk.

Intervention

High-fat diet (HFD, 60% kcal fat) for 12 weeks (in vivo); co-culture of HFD-derived adipose tissue immune cells (macrophages, T cells, dendritic cells) with target cells (in vitro).

Comparator

Normal diet (ND, 10% kcal fat) for 12 weeks (in vivo); monocultures or ND-derived immune cells (in vitro).

Outcome

Expression of adiposity-associated genes, inflammatory markers, and levels of cytokines and chemokines in conditioned culture medium, as well as adipogenesis (lipid accumulation).surrogate

Adipose tissue-resident macrophages from high-fat diet-induced obese mice coordinate with T cells and dendritic cells to stimulate adipocyte differentiation and sustain chronic inflammation.

Limitations

In vitro co-culture may not fully replicate in vivo adipose tissue dynamics
mRNA expression levels may not always accurately predict protein secretion due to post-transcriptional modifications

Abstract

Background: Obesity is one of the major healthcare challenges and socio-economic liabilities worldwide and is rapidly reaching pandemic proportions. Characterized by low-grade chronic inflammation in adipose tissue (AT), the development of obesity is influenced by genetic, neurologic, and metabolic factors, immune activation, and behavioral activities. During obesity, AT macrophages play a central role in inflammation, lipid metabolism, and mitochondrial function in adipocytes. In this study, we investigated how AT resident macrophages, T cells, and dendritic cells (DCs) communicate to coordinate and regulate AT inflammation during obesity. Methods: co-culture of different combinations of AT resident immune cells from mice fed with high-fat diet (HFD) and normal diet (ND) and also 3T3-L1 adipocytes with macrophages, T cells, and DCs isolated from AT of mice fed HFD. We analyzed the expression of adiposity-associated genes, inflammatory markers, and levels of cytokines and chemokine in conditioned culture medium. We also analyzed adipogenesis and performed Oil Red O staining of co-cultured adipocytes to visualize lipid accumulation under these conditions. Results: We found that macrophages from AT derived from HFD-fed mice fueled adipogenesis and inflammation in 3T3-L1 adipocytes and stromal vascular fraction cells derived from ND AT. Macrophages from HFD AT also promoted the expression in ND-derived T cells of chemokines including CCL5 and CXCL10 and inflammatory cytokines including TNF-α, IL-1β, IFN-γ, and IL-17A. Interestingly, T cells from HFD AT also induced expression of inflammatory genes in ND macrophages and lipid accumulation and expression of inflammatory proteins like CXCL2, CCL3, and CCL4 in 3T3-L1 adipocytes. DCs also stimulated adipocyte differentiation, and expression of chemokines and inflammatory cytokines like CCL5, MCP-3, and TNF-α in 3T3-L1 adipocytes. Conclusions: Our findings suggest that during obesity, macrophages work together in a coordinated fashion to modulate the activities of T cells, stimulating adipocyte differentiation, and thereby sustaining chronic inflammation. Thus, macrophages in AT might serve as druggable targets in combatting obesity.

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