The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism

Hebatallah Husseini Atteia; Nora A AlFaris; Ghedeir M Alshammari; Eman Alamri; Salwa Fares Ahmed; Renad Albalwi; Sahar Abdel-Latif Abdel-Sattar

doi:10.3390/foods12234214

The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism

Foods. 2023 Nov 22;12(23):4214. doi: 10.3390/foods12234214.

Authors

Hebatallah Husseini Atteia¹, Nora A AlFaris², Ghedeir M Alshammari³, Eman Alamri⁴, Salwa Fares Ahmed^{5

6}, Renad Albalwi⁴, Sahar Abdel-Latif Abdel-Sattar⁷

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk P.O. Box 47512, Saudi Arabia.
² Department of Physical Sports Sciences, College of Sports Sciences & Physical Activity, Princess Nourah bint Abdulrahman University, Riyadh P.O. Box 84428, Saudi Arabia.
³ Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ Department of Food Science and Nutrition, University of Tabuk, Tabuk P.O. Box 47512, Saudi Arabia.
⁵ Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk P.O. Box 47512, Saudi Arabia.
⁶ Department of Histology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
⁷ Applied College, University of Tabuk, Tabuk P.O. Box 45712, Saudi Arabia.

Abstract

Obesity is the leading cause of non-alcoholic fatty liver disease by provoking hyperglycemia, hyperlipidemia, insulin resistance, oxidative stress, and inflammation. Low activity of AMP-activated protein kinase (AMPK) is linked to obesity, liver injury, and NAFLD. This study involves examining if the anti-steatosis effect of Xanthohumol (XH) in high-fat diet (HFD)-fed rats involves the regulation of AMPK. Adult male rats were divided into five groups (n = 8 each) as control (3.85 kcal/g); XH (control diet + 20 mg/kg), HFD (4.73 kcl/g), HFD + XH (20 mg/kg), and HFD + XH (30 mg/kg) + compound c (cc) (0.2 mg/kg). All treatments were conducted for 12 weeks. Treatment with XH attenuated the gain in body weight, fat pads, fasting glucose, and insulin in HFD rats. It also lowered serum leptin and free fatty acids (FFAs) and improved glucose and insulin tolerances in these rats. It also attenuated the increase in serum livers of liver marker enzymes and reduced serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), FFAs, as well as serum levels of low-density lipoproteins cholesterol (LDL-c) oxidized LDL-c. XH also reduced hepatic levels of malondialdehyde (MDA), nuclear accumulation of NF-κB, and the levels of tumor necrosis-factor-α (TNF-α) and interleukin-6 (IL-6) while stimulating the nuclear levels of Nrf2 and total levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in these HFD-fed rats. At the molecular levels, XH increased hepatic mRNA expression and phosphorylation of AMPK (Thr⁷²) and reduced the expression of lipogenic genes SREBP1c and ACC-1. In concomitance, XH reduced hepatic liver droplet accumulation, reduced the number of apoptotic nuclei, and improved the structures of nuclei, mitochondria, and rough endoplasmic reticulum. Co-treatment with CC, an AMPK inhibitor, completely abolished all these effects of XH. In conclusion, XH attenuates obesity and HFD-mediated hepatic steatosis by activating hepatic AMPK.

Keywords: high-fat diet; inflammation; non-alcoholic fatty liver; oxidative stress; rats; steatosis; xanthohumol.

Grants and funding

This work was funded by the Deanship of Scientific Research at University of Tabuk through Research no. S-1443-0040.