FTO knockdown in rat ventromedial hypothalamus does not affect energy balance.

Margriet A Van Gestel,Roger A H Adan,Mieneke C M Luijendijk,Loek E Sanders,Johannes W De Jong

doi:10.14814/phy2.12152

Margriet A Van Gestel, Roger A H Adan + Show 3 more

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https://doi.org/10.14814/phy2.12152

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Journal: Physiological reports	Publication Date: Dec 1, 2014
Citations: 26	License type: cc-by

Affiliation: University Medical Center Utrecht

Abstract

Single nucleotide polymorphisms (SNPs) clustered in the first intron of the fat mass and obesity‐associated (FTO) gene has been associated with obesity. FTO expression is ubiquitous, with particularly high levels in the hypothalamic area of the brain. To investigate the region‐specific role of FTO, AAV technology was applied to knockdown FTO in the ventromedial hypothalamus (VMH). No effect of FTO knockdown was observed on bodyweight or parameters of energy balance. Animals were exposed twice to an overnight fast, followed by a high‐fat high‐sucrose (HFHS) diet for 1 week. FTO knockdown did not result in a different response to the diets. A region‐specific role for FTO in the VMH in the regulation of energy balance could not be found.

Highlights

Overweight and obesity are increasingly important health problems worldwide
We focused on the role of fat mass and obesity-associated (FTO) on energy balance in the ventromedial hypothalamus (VMH), a hypothalamic nucleus involved in obesity, fear, and female reproductive behavior (Brobeck et al 1943; Mathews and Edwards 1977; Satoh et al 1997; Trogrlic et al 2011)
The plasmids were encapsidated into an AAV1 coat and AAV-miFTO#1 (n = 8), AAV-miFTO#2 (n = 8) and AAV-miLuc (n = 8) were stereotactically injected into the ventromedial hypothalamus

Summary

Introduction

Overweight and obesity are increasingly important health problems worldwide. The World Health Organization reports that 1.4 billion adults are overweight and approximately one-third of them are obese. During 1980 and 2008, obesity rates nearly doubled (Finucane et al 2011). Obesity has been implicated as a major risk factor for cardiovascular diseases (Garrison et al 1987; Manson et al 1995; Ogden et al 2007) and diabetes (Field et al 2001; Oguma et al 2005). Obesity was associated with depression (Luppino et al 2010). An environment that promotes high caloric food intake and discourages physical activity contributes to the occurrence of obesity. Twin and adoptions studies point to a strong genetic basis for the development of obesity (Stunkard et al 1986a,b; MacDonald 1990; Maes et al 1997)

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