HF‐feeding‐induced endoplasmic reticulum stress links metabolic syndrome (1107.11)

This is the authors' abstract. We don't add key points for this paper.

Obesity has been associated with activation of cellular stress signaling and inflammatory pathways. A key player in this cellular stress response is the endoplasmic reticulum (ER). Thus, this study examined the effect of high‐energy/high‐fat (HE/HF)‐induced obesity on ER stress activation. Using male Sprague Dawley rats, we showed that HF feeding activated ER stress response (UPR‐Unfolded Protein Response) in the small intestine, adipose tissue and liver, which was associated with altered gut peptides expression and release including glucagon‐like peptide (GLP‐1), polypeptide YY (PYY) and cholecystokinin (CCK). This effect paralleled increases in weight gain, increased gut permeability, elevated circulating inflammatory cytokines and adipokines levels and impaired calcium homeostasis through disruption of both Sarco(endo)plamsic Ca2+‐ATPase 2b (SERCA), Homocysteine‐inductible endoplasmic reticulum stress protein (HERP) and Der1‐Like Domain Family, Member 1 (DERL2). Further, HF‐diet‐induced ER stress increased systemic inflammation through proinflammatory IKKβ/NF‐κB signaling activation and diminishing insulin sensitivity in the liver tissue. Increased lipogenic and adipogenic enzyme expression were also observed in the liver and adipose tissue of HF‐fed animals. Our findings suggest that HF feeding results in profound dysfunctions of ER homeostasis promoting weight gain and increased adiposity, all of which may contribute to perpetuation of obesity.