Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation

Josimar Macedo de Castro; Dirson João Stein; Helouise Richardt Medeiros; Carla de Oliveira; Iraci L S Torres

doi:10.3389/fnut.2021.648893

Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss Without Altering Muscle Mass in Obese Rats Under Calorie Restriction: A Preliminary Investigation

Front Nutr. 2021 Sep 13:8:648893. doi: 10.3389/fnut.2021.648893. eCollection 2021.

Authors

Josimar Macedo de Castro^{1

2

3}, Dirson João Stein^{1

2

3}, Helouise Richardt Medeiros^{1

2

3}, Carla de Oliveira⁴, Iraci L S Torres^{1

2

3}

Affiliations

¹ Postgraduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
² Laboratory of Pain Pharmacology and Neuromodulation: Preclinical Studies, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
³ Animal Experimentation Unit, Grupo de Pesquisa e Pós-Graduação, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁴ Faculdade São Francisco de Assis (UNIFIN), Porto Alegre, Brazil.

Abstract

Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation. Therefore, we aimed to investigate the effects of CR on SMT and on hypothalamic inflammatory biomarkers in obese adult male Wistar rats, and whether NR supplementation alone or in combination with CR affects these parameters. Obesity was induced in rats through a cafeteria diet for 6 weeks. After that, a group of obese rats was exposed to CR, associated or not associated with NR supplementation (400 mg/kg), for another 4 weeks. As a result, obese rats, with or without CR, presented lower relative weight of SMT when compared with eutrophic rats. Rats under CR presented lower absolute SMT weight compared with obese and eutrophic rats, in addition to presenting elevated hypothalamic levels of TNF-α. NR supplementation, in all groups, enhanced weight loss and increased relative weight of the SMT. Furthermore, in animals under CR, NR reversed increases TNF-α levels in the hypothalamus. In this study, these data, although succinct, are the first to evidence the effects of NR on SMT and neuroinflammation when associated with CR, especially in obesity conditions. Therefore, this provides preliminary support for future studies in this investigative field. Furthermore, NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.

Keywords: brain; caloric restriction; hypothalamus; muscle mass; neuroinflammation; nicotinamide riboside; obesity; skeletal muscle tissue.