Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats.

Marina Martín,Victoria Catalán,Beatriz Ramírez,Carlos Diéguez,Sara Becerril,Miguel López,Javier Gómez-Ambrosi,Gema Frühbeck,María A Burrell,Amaia Rodríguez

doi:10.3390/nu13072128

Abstract

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.

Highlights

Obesity constitutes a persistent major health concern linked to increased morbidity and mortality [1]
Groups fed ad libitum experienced a more pronounced percentage of body weight increase than the corresponding groups subjected to caloric restriction (p < 0.0001)
Data from our study suggest that the distribution and the morphology of white adipose tissue (WAT) have to be considered when assessing glucose homeostasis and obesity

Summary

Introduction

Obesity constitutes a persistent major health concern linked to increased morbidity and mortality [1]. Dietary interventions should be personalized, adapted to food preferences and enable flexible approaches to reduce calorie intake in order to strengthen motivation and adherence of patients with obesity [3]. In this regard, several control studies have shown that low-carbohydrate, high-fat diets (HFD) in patients with obesity and diabetes induce short-term favorable effects on weight loss, blood glucose and insulin [4]. Caloric restriction alleviates multiple complications of obesity and aging, including insulin resistance, dyslipidemia, hypertension, atherosclerosis and systemic inflammation [5,6] It is not clear whether weight loss caused by a restricted HFD is accompanied by modifications in signals involved in the regulation of body weight and energy homeostasis

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Conclusion