Hepatic steatosis induced by nicotine plus Coca-Cola™ is prevented by nicotinamide riboside (NR)

Front Endocrinol (Lausanne). 2024 May 2:15:1282231. doi: 10.3389/fendo.2024.1282231. eCollection 2024.

Abstract

Introduction: Cigarettes containing nicotine (Nic) are a risk factor for the development of cardiovascular and metabolic diseases. We reported that Nic delivered via injections or e-cigarette vapor led to hepatic steatosis in mice fed with a high-fat diet. High-fructose corn syrup (HFCS) is the main sweetener in sugar-sweetened beverages (SSBs) in the US. Increased consumption of SSBs with HFCS is associated with increased risks of non-alcoholic fatty liver disease (NAFLD). Nicotinamide riboside (NR) increases mitochondrial nicotinamide adenine dinucleotide (NAD+) and protects mice against hepatic steatosis. This study evaluated if Nic plus Coca-Cola™ (Coke) with HFCS can cause hepatic steatosis and that can be protected by NR.

Methods: C57BL/6J mice received twice daily intraperitoneal (IP) injections of Nic or saline and were given Coke (HFCS), or Coke with sugar, and NR supplementation for 10 weeks.

Results: Our results show that Nic+Coke caused increased caloric intake and induced hepatic steatosis, and the addition of NR prevented these changes. Western blot analysis showed lipogenesis markers were activated (increased cleavage of the sterol regulatory element-binding protein 1 [SREBP1c] and reduction of phospho-Acetyl-CoA Carboxylase [p-ACC]) in the Nic+Coke compared to the Sal+Water group. The hepatic detrimental effects of Nic+Coke were mediated by decreased NAD+ signaling, increased oxidative stress, and mitochondrial damage. NR reduced oxidative stress and prevented mitochondrial damage by restoring protein levels of Sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor coactivator 1-alpha (PGC1) signaling.

Conclusion: We conclude that Nic+Coke has an additive effect on producing hepatic steatosis, and NR is protective. This study suggests concern for the development of NAFLD in subjects who consume nicotine and drink SSBs with HFCS.

Keywords: NAD+; hepatic steatosis; high-fructose corn syrup; nicotinamide riboside; nicotine.

MeSH terms

  • Animals
  • Fatty Liver / chemically induced
  • Fatty Liver / metabolism
  • Fatty Liver / prevention & control
  • High Fructose Corn Syrup / adverse effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Niacinamide* / analogs & derivatives
  • Niacinamide* / pharmacology
  • Nicotine*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control
  • Oxidative Stress / drug effects
  • Pyridinium Compounds* / pharmacology

Substances

  • nicotinamide-beta-riboside

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. NIMHD funded CDU Accelerating Excellence in Translational Research (AXIS) grant # U54MD007598. National Center for Advancing Translational Sciences UCLA CTSI # UL1TR001881. NIGMS grant # SC2GM135127. NIMHD Grant # S21-MD000103. Voucher support from the NIH Accelerating Excellence in Translational Science (AXIS) grant # 5U54MD007598. NIGMS grant # SC2GM125551. NIH R25 # DA050723. California TRDRP grant # 28CP-0040. DOD CDMRP grant # PR190942.