Aim:
Background: Obesity is a widespread public health problem that affects people of all age groups. It has significant societal and economic influences. Obesity significantly increases likelihood of developing many non-communicable diseases, such as sleep apnea, osteoarthritis, gout, dyslipidemia, gallbladder disease, type 2 diabetes, coronary heart disease, hypertension, and stroke. Tirzepatide is a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist recommended for people with T2DM to manage their blood sugar levels along with diet and exercise. Aims: to examine potential protective effect of Tirzepatide against obesity-induced metabolic dysfunction and hepatic inflammatory and apoptotic responses.

Material and methods:
Materials and method: A total of 28 adult male Sprague-Dawley rats were employed and divided into four groups, normal control group involved seven rats fed a regular diet, while other rats received a high fat diet. Obese rats were separated into three groups after eight weeks of high fat diet: obesity, Tirzepatide (10 nmol/kg) s.c and vehicle groups, and treated for four weeks. Data regarding body weight, blood glucose, serum insulin, liver enzymes, and TNF-α, IL-1β and caspase-3 levels in the liver tissue were obtained.

Results:
results revealed that Tirzepatide-treated obese rats exhibited significantly reduced body weight, blood glucose, serum insulin ALT, triglyceride, VLDL levels. Additionally, liver specimens from Tirzepatide group demonstrated lower levels of TNF-α, IL-1β and caspase-3 compared to obese untreated rats.

Conclusions:
It concluded that Tirzepatide treatment mitigates the metabolic dysregulations induced by High Fat Diet, additionally; it ameliorates the inflammatory and apoptotic responses in hepatic tissue triggered by High Fat Diet.