Elderly rats fed with a high-fat high-sucrose diet developed sex-dependent metabolic syndrome regardless of long-term metformin and liraglutide treatment

Front Endocrinol (Lausanne). 2023 Oct 20:14:1181064. doi: 10.3389/fendo.2023.1181064. eCollection 2023.

Abstract

Aim/introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes.

Methods: Elderly Sprague-Dawley rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old.

Results: Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes.

Conclusion: Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females.

Keywords: diabetes mellitus; high-fat high-sucrose diet; insulin resistance; metabolomics; sex differences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Liraglutide* / therapeutic use
  • Male
  • Metabolic Syndrome* / drug therapy
  • Metabolic Syndrome* / etiology
  • Metformin* / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors
  • Sucrose / adverse effects

Substances

  • Hypoglycemic Agents
  • Liraglutide
  • Metformin
  • Sucrose

Grants and funding

This study was supported by the RECOOP-CSMC Fusion Research Grant No. 029 2015-2021 “Obesity and Diabetes”, and by the Ministry of Human Capacities [Hungary grant 20391-3/2018/FEKUSTRAT]. This study was supported in part with the following grants: Croatian Science Foundation grants to MH (Raft tuning, IP-2014-09-2324), RS (IP-2016-06-6545), and SG (RepairStroke, IP-06-2016-1892); Josip Juraj Strossmayer University of Osijek, Faculty of Medicine institutional grant to MH (Lipid profile of metabolic stress, IP9-2019); Josip Juraj Strossmayer University of Osijek grant to MH (INGI-2015-35) and VI (UNIOS-ZUP 2018-44); and European Union through the European Regional Development Fund, Operational Programme “Competitiveness and Cohesion 2014-2020”, grant agreement No. KK.01.1.1.01.0007, CoRE – Neuro, and grant agreement No. KK.01.1.1.02.0015, “Research and diagnostics of malignant, infectious and rare metabolic diseases based on MALDI TOF technology”.