Effects of an High-Fat Diet Enriched in Lard or in Fish Oil on the Hypothalamic Amp-Activated Protein Kinase and Inflammatory Mediators.

Emanuela Viggiano,Maria Pina Mollica,Marcellino Monda,Giovanna Trinchese,Bruno De Luca,Sergio Chieffi,Antonio Barletta,Gina Cavaliere,Marianna Crispino,Lillà Lionetti,Chiara De Filippo,Marcello Gaita

doi:10.3389/fncel.2016.00150

Abstract

The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (ω)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in ω3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKβ, TNF-α) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia.

Highlights

Obesity and diabetes are major causes of morbidity and mortality in the western world, and may lead to inflammatory responses and oxidative stress in the peripheral tissues (Hotamisligil, 2006)
The present study aims to evaluate the effect of the nutritional substitution of saturated by unsaturated fatty acids on the modulation of hypothalamic inflammation in obesity
Our data confirmed that the extent of high fat diet (HFD) harmful effects depends on the type of fat included in the diet and in particular, the HFDs rich in poly-unsaturated fatty acids are less deleterious than those rich in saturated fat

Summary

INTRODUCTION

Obesity and diabetes are major causes of morbidity and mortality in the western world, and may lead to inflammatory responses and oxidative stress in the peripheral tissues (Hotamisligil, 2006). Several studies have demonstrated that AMPK in the hyphotalamus regulates food intake and that its activity is modulated by several hormones such as leptin, adiponectin and insulin. Whereas leptin inhibits AMPK activity in the arcuate and in the paraventricular nuclei of hypotalamus, insulin is known to inhibit AMPK activity in the lateral, ventromedial, and dorsomedial hypothalamic regions (Minokoshi et al, 2004) All these brain regions are involved in the control of food intake (Monda et al, 1993; Viggiano et al, 2006) and in energy expenditure (Monda et al, 1996; Messina et al, 2013). We have analyzed, in the same animals, the involvement of insulin, leptin and inflammatory parameters in the modulation of AMPK

MATERIALS AND METHODS

Ethics Statement

RESULTS

Findings

DISCUSSION