Asiedu, BerniceLembede, Busisani WisemanGomes, Monica N.Kasonga, Abe E.Nkomozepi, PilaniNyakudya, Trevor TapiwaChivandi, Eliton2023-03-302023-03-302023-01Asiedu, B.; Lembede, B.W.; Gomes, M.; Kasonga, A.; Nkomozepi, P.; Nyakudya, T.T.; Chivandi, E. Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models. Metabolites 2023, 13, 167. https://doi.org/10.3390/metabo13020167.2218-1989 (online)10.3390/metabo13020167http://hdl.handle.net/2263/90272Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague–Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12–21: group 1—nutritive milk (NM), group 2—NM +1 g/kg ethanol (Eth), group 3—NM + 40 mg/kg ZO, group 4—NM + Eth +ZO. From PND 46–100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD.en© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Alcohol-induced fatty liver disease (AFLD)ZingeroneMacrosteatosisSterol regulatory element binding protein 1c (SREBP1c)Peroxisome proliferator activator receptor-alpha (PPAR-α)Article