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Cell Stress. 2019 Jan 25;3(2):29-37. doi: 10.15698/cst2019.02.174.

Could de-stressing the brain be the solution for long-term weight loss?

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Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, 97080 Bavaria, Germany.
Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, 97080 Bavaria, Germany.


The obese brain is stressed and inflamed. This is mainly at the level of neurons and glial cells in the hypothalamus: a brain region where the adipokine leptin acts to control feeding and body weight. Relieving hypothalamic neuronal endoplasmic reticulum (ER) stress with the natural small molecule drugs celastrol or withaferin-A reverses the leptin resistance commensurate with obesity, producing a degree of weight loss found only with bariatric surgery. Here, recent evidence from rodent models of vertical sleeve gastrectomy (VSG) is brought to the fore which suggests that this particular bariatric surgical procedure may work in a similar fashion to celastrol and withaferin-A alongside remedying hypothalamic inflammation and gliosis. Thus, restoring and preserving healthy hypothalamic neuronal and glial cell function, be it by pharmacological or surgical means, ensures a negative energy balance in an environment constructed to promote a one - possibly through re-establishing communication between adipose tissue and the brain.


endoplasmic reticulum stress; gliosis; hypothalamus; inflammation; leptin resistance; obesity; vertical sleeve gastrectomy

Conflict of interest statement

Conflict of interest: The authors have no conflicts of interest to declare.

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