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

Florian Seyfried,Mohammed K Hankir

doi:10.15698/cst2019.02.174

Abstract

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.

Highlights

One just needs to take a look at a typical vending machine to appreciate what has happened to our food and drink
ADIPOSE TISSUE AND INTESTINAL INFLAMMATION AS A CAUSE OF INSULIN RESISTANCE Early efforts to disentangle the close relationship between obesity and type II diabetes focused on the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in visceral white adipose tissue [1]
Subsequent rodent studies revealed in reverse chronological order that during obesity progression, antigen-presenting and IgG-releasing B cells are the first to arrive in visceral white adipose tissue (vWAT), possibly attracted by chemokines released from swelling adipocytes sensed by the mechanoreceptor transient receptor potential vanilloid 4 (TRPV4) [2], followed by the recruitment of cytotoxic CD8+ T cells and by M2 macrophages [3, 4,5]

Summary

Introduction

One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. 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.

Results

Conclusion