Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake.
Laura Liñares-PoseEva Rial-PensadoÁnxela Estévez-SalgueroEdward MilbankIsmael González-GarcíaClaudia RodríguezPatricia Seoane-CollazoNoelia Martinez-SánchezRubén NogueirasDolores PrietoCarlos DiéguezCristina ContrerasMiguel LópezPublished in: Genes (2018)
Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity. Herein, we also demonstrated that this body weight decrease was more likely associated with an increased BAT thermogenesis and browning of white adipose tissue (WAT) than to anorexia. Overall, these results indicate that the modulation of GRP78 in the VMH may be a target against obesity.
Keyphrases
- adipose tissue
- insulin resistance
- high fat diet
- high fat diet induced
- endoplasmic reticulum stress
- protein kinase
- metabolic syndrome
- body weight
- type diabetes
- weight loss
- cell surface
- skeletal muscle
- endoplasmic reticulum
- binding protein
- weight gain
- high glucose
- diabetic rats
- big data
- electronic health record
- gene expression
- genome wide
- copy number
- endothelial cells
- poor prognosis
- glycemic control
- oxidative stress
- protein protein
- drug induced
- dna binding
- deep learning
- heat shock protein