Effect of Weight Management on AMPK Activation in the Adjunctive Treatment of Endometrial Cancer

Obesity is an important risk factor for endometrial cancer and may influence the response to progestin-based fertility-sparing treatment through insulin resistance, hormonal dysregulation, and chronic inflammation. Current clinical guidelines recommend weight management for patients undergoing fertility-sparing treatment. However, further prospective evidence is needed to determine whether comprehensive lifestyle interventions can improve pathological response in overweight or obese patients with endometrial cancer. The DEAR framework integrates dietary management, physical activity, family and healthcare support, and sleep and stress management to improve metabolic health and promote sustainable lifestyle changes. AMP-activated protein kinase (AMPK), a key regulator of cellular energy metabolism, may be involved in metabolic regulation and progestin sensitivity. However, the relationship between lifestyle-induced metabolic changes, AMPK, and tumor response remains unclear. Therefore, this study aims to evaluate the clinical value of DEAR-based comprehensive weight management as an adjunct to fertility-sparing treatment and explore the association between metabolic regulation and treatment response.

• DEAR-Based Comprehensive Weight Management (Behavioral): Participants will receive a 12-week comprehensive weight management program based on the DEAR principles of Diet, Exercise, Accompany, and Refresh. The program includes an intermittent fasting diet and aerobic exercise three times per week, along with family and healthcare support, sleep monitoring, and stress management.
• Balanced Diet and Self-Directed Exercise (Behavioral): Participants will receive a balanced diet and engage in self-directed exercise for 12 weeks. They will be encouraged to engage in physical activity independently according to their individual circumstances, while also receiving support from family members and healthcare professionals, sleep monitoring, and stress-management support.

Primary outcomes

• Pathological Complete Response Rate [6 months of intervention]: Pathological complete response is defined as the absence of residual atypical endometrial hyperplasia or endometrioid adenocarcinoma on histopathological examination following fertility-sparing treatment, as confirmed by pathologists.

Secondary outcomes

• Body Mass Index [6 months of intervention]: Use the Inbody720 to measure height and weight and calculate BMI according to the formula"BMI (= weight (kg)/height² (m²)".
• Change in Serum AMP-Activated Protein Kinase (AMPK) Levels [6 months of intervention]: Serum AMP-activated protein kinase (AMPK) concentrations will be measured using an enzyme-linked immunosorbent assay (ELISA).
• Time to Pathological Complete Response [6 months of intervention]: Time to pathological complete response will be defined as the interval from randomization to the first histopathological confirmation of complete response following fertility-sparing treatment.
• Disease Recurrence Rate [6 months of intervention]: The proportion of participants with histopathologically confirmed disease recurrence after achieving pathological complete response during the follow-up period.
• Time to Disease Recurrence [6 months of intervention]: Time to disease recurrence will be defined as the interval from the first documented pathological complete response to the first histopathologically confirmed disease recurrence.
• triglycerides [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• cholesterol [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• high density lipoprotein [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• low density lipoprotein [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• fasting glucose [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• glycated hemoglobin [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.
• fasting insulin [6 months of intervention]: About 5 ml of venous blood was drawn from the study subjects in the fasting state in the morning and sent to the Laboratory Department of the People's Hospital of Peking University, where it was measured by Beckman AU5800 biochemical analyzer.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Aged 18 years or older.
* Diagnosed with endometrial cancer.
* Have undergone immunohistochemical staining of pathological tissue samples and sequencing analysis.
* Receiving fertility-sparing treatment.
* Body mass index ≥ 24 kg/m².
* Provided written informed consent to participate in the study.

Exclusion Criteria:

* Patients with communication difficulties.
* Pregnant patients.
* Patients with severe medical or surgical comorbidities, including urinary tract stones, a history of renal failure or severe renal impairment, familial dyslipidemia, severe liver disease, chronic metabolic acidosis, a history of pancreatitis, severe diabetes mellitus, active gallbladder disease, disorders of fat digestion, severe cardiovascular disease, cerebrovascular disease, or other serious comorbidities.

• Xiaodan Li, Study chair, Peking University People's Hospital