Adiponectin replacement
therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how
adiponectin acts against Metabolic-associated
Fatty Liver Disease (MAFLD) and
Nonalcoholic Steatohepatitis (NASH). However, the pharmacological limitations of the intact
protein have prompted a focus on alternative options, specifically peptidic and small molecule agonists targeting the
adiponectin receptor.
AdipoRon is an extensively researched non-peptidic
drug candidate in
adiponectin replacement
therapy. In turn,
ADP355 is an
adiponectin-based active short
peptide. They have garnered significant attention due to their potential as substitutes for
adiponectin. Researchers have studied
AdipoRon's and
ADP355's efficacy and therapeutic applications in various disease conditions. However, the effects of
AdipoRon and
ADP355 against
NAFLD and NASH models advanced more, and no systematic review explored this area before. This systematic review was conceived to address the deficiency mentioned above and consider the lack of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (
PRISMA) guidelines were utilized. To assess the risk of bias in systematic review, The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed. Results from pre-clinical evidence show that
AdipoRon and
ADP355 represent promising effects in
NAFLD and NASH-related models, including reducing hepatic steatosis, modulating
inflammation, improving
insulin sensitivity, enhancing mitochondrial function, and protecting against
liver fibrosis. While
AdipoRon and
ADP355 exhibit promise in pre-clinical studies and experimental models, additional clinical trials are necessary to assess their effectiveness, safety, and potential translational therapeutic potential uses in
NAFLD and NASH human cases.