Abstract
Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr −/−.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (−17%) and hepatic steatosis (−22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.
Highlights
Worldwide, the prevalence of overweight and obesity in both adults and children has increased dramatically over the last decades and has become a major health concern [1]
Nicotinamide riboside treatment in the nicotinamide riboside (NR) and COMBI groups significantly elevated plasma nicotinamide levels to 1.9 ± 0.1 relative units (RU) and 1.9 ± 0.3 RU, respectively. These data show that dietary supplementation with LC and NR in an high-fat diet (HFD) resulted in a Innt.oJr.mMaoll.izScait. i2o0n19,o2r0, 4m35o9dest increase of the respective circulating metabolites, indicating eff3ecotfi1v6e delivery into the circulation
The objective of the present study was to evaluate the anti-obesogenic and hepatoprotective effects of a novel treatment using a combination of LC and NR
Summary
The prevalence of overweight and obesity in both adults and children has increased dramatically over the last decades and has become a major health concern [1]. Adiposity and ectopic fat accumulation are characteristics of obesity that can cause comorbidities. In recent years non-alcoholic fatty liver diseases (NAFLD) has emerged as the most common chronic liver disease associated with obesity [2]. Current concepts for treatment of obesity focus on lifestyle changes and include dietary advice combined with exercise. Despite lifestyle and dietary advice, obesity rates have not declined in the last three decades [1]. Current treatments are insufficient to accomplish sustained weight loss for the majority of obese patients [3]. There is a need for new strategies that stimulate energy metabolism in other ways [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
