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

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.

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

“…Benefits of NR supplementation have also been described in animal models of muscle disorders, such as models of mitochondrial myopathies [ 12 , 13 ] and of muscular dystrophy characterized by muscle wasting [ 14 , 15 ]. Furthermore, NR treatment improves muscle quality and physical performance in middle-aged mice [ 16 ] and preserves muscle mass during weight loss in obese rats under calorie restriction [ 17 ]. The positive outcomes of these and other pre-clinical studies are prompting human trials assaying the impact of NR supplementation on a variety of metabolic and exercise-related end-points in healthy adults, old persons, and persons with obesity, with disparate results so far [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet

“…These results were unsurprising because most previous studies reported no changes in these variables [ 26 , 40 , 41 ]. In cases where ω-3 PUFA supplementation modified anthropometric parameters, the treatment administration period was longer than six months or was complemented with physical activity, dietary, and pharmacological therapy [ 25 , 42 , 43 ].…”

“…The deep muscular plane of the leg was identified, and the soleus skeletal muscle was dissected (following the natural lines), separating it from the underlying tendons to determine absolute weight. Subsequently, the relative weight was calculated with the absolute weight of the soleus muscle (g)/Body weight (g) × 100 [ 25 ]. Finally, the soleus skeletal muscle was stored at −30 °C with QIAzol lysis reagent for later processing.…”

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives

“…NRS provided daily to suckling male mice improved lipid and energy metabolism in skeletal muscle and liver in adulthood, correlated with an upregulation of SIRT1 and AMP-dependent protein kinase signaling pathways [ 153 ]. In obese rats under CR, NRS (400 mg/kg for four weeks) neutralized hypothalamic inflammation by reverting high levels of TNF-α and increases weight loss without altering skeletal muscle mass [ 154 ]. Further, high doses (9 g/kg diet) of NRS for 18 weeks induced glucose intolerance and WAT dysfunction in male C57BL/6JRccHsd mice fed a mildly obesogenic diet (MOD) containing low but adequate tryptophan [ 155 , 156 , 157 ].…”