Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates Diet-induced Endoplasmic Reticulum Stress in Liver and Adipose Tissue
Year: 2013
Type: article
Abstract: Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has beneficial effects in cardiovascular, inflammatory, and metabolic diseases in murine models. Mice with targeted deletion or pharmacological inhibition of sEH exhibit improved insulin signaling in liver and adipose tissue. Herein, we assessed the role of sEH in regulating endoplasmic reticulum (ER) stress in liver and adipose tissue. We report that sEH expression was increased in the livers and adipose tissue of mice fed a high fat diet, the adipose tissue of overweight humans, and palmitate-treated cells. Importantly, sEH deficiency or inhibition in mice attenuated chronic high fat diet-induced ER stress in liver and adipose tissue. Similarly, pharmacological inhibition of sEH in HepG2 cells and 3T3-L1 adipocytes mitigated chemical-induced ER stress and activation of JNK, p38, and cell death. In addition, insulin signaling was enhanced in HepG2 cells treated with sEH substrates and attenuated in cells treated with sEH products. In summary, these findings demonstrate that sEH is a physiological modulator of ER stress and a potential target for mitigating complications associated with obesity.
Source: Journal of Biological Chemistry
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G1225459562, G1251846919, Role of adipose protein-tyrosine phosphatase 1B in glucose homeostasis and body m, G2366971526, G3068097868, Epoxyeicosanoids and Renal Vascular Function in Obesity & Hypertension, HYDROLYTIC ENZYMES IN THE METABOLISM OF TOXINS, G549601326, Hydrolytic enzymes in the metabolism of toxins, Role of Protein-Tyrosine Phosphatase 1B in Pancreatic Islet Function, G7346897736
OpenAlex ID: W2140116636