Regulation of Adipsin Expression by Endoplasmic Reticulum Stress in Adipocytes

Abstract

Adpsin is an adipokine that stimulates insulin secretion from β-cells and improves glucose tolerance. Its expression has been found to be markedly reduced in obese animals. However, it remains unclear what factors lead to downregulation of adipsin in the context of obesity. Endoplasmic reticulum (ER) stress response is activated in various tissues under obesity-related conditions and can induce transcriptional reprogramming. Therefore, we aimed to investigate the relationship between adipsin expression and ER stress in adipose tissues during obesity. We observed that obese mice exhibited decreased levels of adipsin in adipose tissues and serum and increased ER stress markers in adipose tissues compared to lean mice. We also found that ER stress suppressed adipsin expression via adipocytes-intrinsic mechanisms. Moreover, the ER stress-mediated downregulation of adipsin was at least partially attributed to decreased expression of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor in the regulation of adipocyte function. Finally, treatment with chemical chaperones recovered the ER stress-mediated downregulation of adipsin and PPARγ in vivo and in vitro. Our findings suggest that activated ER stress in adipose tissues is an important cause of the suppression of adipsin expression in the context of obesity.

Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)

“…Although these results are somewhat conflicting with respect to those obtained by immunohistochemistry, they could be explained by the lower expression of PPARG and CEBPA regulatory genes observed in the patients’ samples, a scenario consistent with lipoatrophy ( Table 2 ) [ 42 ]. In agreement with this, the down-regulation of PPARG may be the main causative event of the coordinate impairment in the expression of CFD and C3 genes, which are known targets of PPARG -dependent regulation [ 43 , 44 ]. Correspondingly, if the tissue sample was obtained at an advanced stage of lipodystrophy, the expression of complement genes may be significantly influenced by down-regulation of PPARG and CEBPA .…”

TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

“…Among the gene processes that were modulated in TGFBI KO mice, we focused on the signi cantly enriched complement and coagulation cascades. Adipsin is a regulatory protein of the complement cascade whose expression is downregulated in mice with acquired metabolic diseases 25 . Consistently, the expression of adipsin was reduced in HFD-fed obese mice compared with ND-fed normal mice (Supplementary Fig.…”

Adipsin – summing up large-scale results: A review

“…По данным K. Ryu и соавт., на секрецию адипсина негативно влияет стресс эндоплазматического ретикулума в адипоцитах, предположительно за счет подавления рецепторов, активируемых пероксисомным пролифератором (PPARγ), которые имеют ключевое значение для дифференцировки адипоцитов и продукции адипокинов [24]. Авторы считают, что ингибирование стресса эндоплазматического ретикулума в адипоцитах потенциально может быть использовано в качестве способа лечения и профилактики β-клеточной недостаточности у пациентов с сахарным диабетом.…”