No abstract

Exercise training reduces systemic and adipose tissue inflammation. However, these beneficial effects seem to be largely tied to reductions in adipose tissue mass. The purpose of the present study was to determine if exercise training confers a protective effect against an acute inflammatory challenge. We hypothesized that the induction of inflammatory markers, such as interleukin 6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), and TNF-α by the beta-3 adrenergic agonist CL 316,243 would be reduced in adipose tissue from trained mice and this would be associated with reductions in transient receptor potential cation channel 4 (TRPV4), a protein recently shown to regulate the expression of proinflammatory cytokines. Exercise training (4 wk of treadmill running, 1 h/day, 5 days/wk) increased markers of skeletal muscle mitochondrial content and the induction of PPAR-gamma coactivator 1 alpha in epididymal adipose tissue. The mRNA expression of IL-6, SOCS3, and TNFα were not different in subcutaneous and epididymal adipose tissue from sedentary and trained mice; however, the CL 316,243-mediated induction of these genes was attenuated ∼50% in epididymal adipose tissue from trained mice as were increases in plasma IL-6. The effects of training were not explained by reductions in lipolytic responsiveness, but were associated with decreases in TRPV4 protein content. These results highlight a previously unappreciated anti-inflammatory effect of exercise training on adipose tissue immunometabolism and underscores the value of assessing adipose tissue inflammation in the presence of an inflammatory insult.

The results suggest a link between exercise-induced increases in IL-6, reductions in indices of M1 macrophages, and increased IL-10, a reputed anti-inflammatory cytokine with insulin-sensitizing properties.

Mitochondrial enzyme expression is reduced in adipose tissue from old mice, yet little is known regarding mechanisms that could be mediating, or interventions that could be used, to reverse these changes. The purpose of this study was to examine the relationship between lipolytic and fatty acid reesterification enzymes, 5' adenosine monophosphate-activated protein kinase and mitochondrial proteins in adipose tissue from young versus old mice. A second aim was to determine whether metformin treatment could rescue the age-associated decline in adipose tissue mitochondrial proteins. Approximately 22-month-old male C57BL/6 mice were fed a diet with or without 0.5% metformin for 8 weeks. Compared with young mice (~11 wk of age), the protein content/phosphorylation of hormone-sensitive lipase, adipose tissue triglyceride lipase, and phosphoenolpyruvate carboxykinase were reduced in old mice. This was paralleled by increases in the plasma nonesterified fatty acid:glycerol ratio and reductions in adipose tissue 5' adenosine monophosphate-activated protein kinase activity and select mitochondrial proteins in old mice. There were no differences in these variables when comparing adipose tissue from young and 6-month-old mice. While metformin improved glucose homeostasis, it did not increase 5' adenosine monophosphate-activated protein kinase phosphorylation or mitochondrial enzymes. Our findings demonstrate a co-ordinated down regulation of lipolytic, reesterification, and mitochondrial enzymes in adipose tissue with aging that is unresponsive to metformin treatment.

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.