Obesity‐induced inflammation contributes to the development of obesity‐related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity‐induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high‐fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription‐PCR and enzyme‐linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type‐1 (TRPV‐1), peroxisome proliferator–activated receptor (PPAR)‐α, and PPARγ coactivator‐1α (PGC‐1α) mRNAs were also measured by RT‐PCR, and PPARα luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor‐α (TNFα), monocyte chemoattractant protein‐1 (MCP‐1), and interleukin (IL)‐6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV‐1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARα/PGC‐1α mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARα. Our data suggest that dietary capsaicin may reduce obesity‐induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARα and TRPV‐1 expression/activation.

Tsuyoshi Goto, Joo-Young Lee, Aki Teraminami, Yong-Il Kim, Shizuka Hirai, Taku Uemura, Hiroyasu Inoue, Nobuyuki Takahashi, Teruo Kawada

Brown adipose tissue (BAT) plays a central role in regulating energy homeostasis and may provide novel strategies for the treatment of human obesity. BAT-mediated thermogenesis is regulated by mitochondrial uncoupling protein 1 (UCP1) in classical brown and ectopic beige adipocytes and is controlled by sympathetic nervous system (SNS). Previous work indicated that fish oil intake reduces fat accumulation and induces UCP1 expression in BAT; however, the detailed mechanism of this effect remains unclear. In this study, we investigated the effect of fish oil on energy expenditure and the SNS. Fish oil intake increased oxygen consumption and rectal temperature, with concomitant upregulation of UCP1 and the β3 adrenergic receptor (β3AR), two markers of beige adipocytes, in the interscapular BAT and inguinal white adipose tissue (WAT). Additionally, fish oil intake increased the elimination of urinary catecholamines and the noradrenaline (NA) turnover rate in interscapular BAT and inguinal WAT. Furthermore, the effects of fish oil on SNS-mediated energy expenditure were abolished in transient receptor potential vanilloid 1 (TRPV1) knockout mice. In conclusion, fish oil intake can induce UCP1 expression in classical brown and beige adipocytes via the SNS, thereby attenuating fat accumulation and ameliorating lipid metabolism.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)–mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.