2.2. SREBP1-
In the livers of HFHS mice, ob/ob mice, db/db mice, and also the individuals with NAFLD, FOXO3 expressions were elevated. In HepG2 cells, FOXO3 overexpression enhanced cellular TG concentrations while FOXO3 knockdown decreased them. In C57BL/6 J mice on a chow diet, gain-of-function of FOXO3 led to the deposition of hepatic TG, also when a high-fat diet is given, it exacerbated hepatic steatosis. The enhanced expression of TG synthesis-related genes such as SREBP1c, in the liver of mice, was determined by transcript analysis. In a mechanism-based manner, FOXO3 knockdown decreased SREBP1c expression while FOXO3 overexpression increased it. SREBP1c modulated the transcription of the SREBP1c promoter, according to luciferase reporter tests. By encouraging the SREBP1c promoter’s transcriptional activity, FOXO3 increases TG formation along with its hepatic accumulation (Wang et al., 2019). There is proof that diets high in saturated fat, like those high in palmitate, stimulate the development of Aβ, the histological sign of AD. The mechanisms underlying the harmful consequences of a diet high in palmitate on the stimulation of Aβ genesis have not yet been fully understood. The gene expressions which code for the protein intricated in nearly every aspect of lipid metabolism are regulated by the transcription factor sterol response element binding protein 1 (SREBP1), which is altered by saturated fatty acids like palmitate. The study established how alterations in SREBP1 expression as well as in transcription contributed to the impacts that palmitate had on Aβ genesis along with on Beta-secretase 1(BACE1) expression. This research identifies SREBP1 activation as a unique molecular factor in the upregulation of BACE1 expression brought on by palmitate and subsequent Aβ generation. However, the role of SREBP1 in AD linked with liver disorder is not well understood on the molecular level. But up to the present work, no molecular research had yet suggested that SREBP1 dysregulation was responsible for the regulation of AD-related processes (Marwarha et al., 2019). Age-related disorders including AD and glucose and lipid homeostasis have both been linked to FOXOs. Significant metabolic abnormalities in the brain are also present in AD. Misregulation of the FOXO signaling pathway may be the cause of age-related functional decline and age-related illnesses due to its important involvement in metabolic balance and organismal lifespan (Du et al., 2021). However, FOXO has a significant role in the development of liver diseases like NAFLD, which is not well understood. In the above-concluded studies, the experiments were designed to examine the effects of FOXO modulation in liver-associated AD. Thus, it can be said that FOXO has a beneficial role in protecting the fatty liver disease induced by diet (Pan et al., 2017). Whereas, this expression of inflammation might lead to the development of AD and FOXO might play a protective role in it. However, no molecular studies have been implicated yet.