Effect of combined metformin and Lactobacillus plantarum DAD-13 administration on the Lee index, lipid profile, and visceral adipose tissue histopathology in a rat model of NAFLD

Syifa  Mustika; Achmad  Rudijanto; Muchammad  Kamal Hadi; Holipah; Suri  Nurtsalits Nabisah; Nabila  Salsabila; Putu  Ijiya Danta Awatara

Authors

Syifa Mustika Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Achmad Rudijanto Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Muchammad Kamal Hadi Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Holipah Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
Suri Nurtsalits Nabisah Undergraduate Medical Program, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
Nabila Salsabila Undergraduate Medical Program, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
Putu Ijiya Danta Awatara Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia

Keywords:

Adipocyte diameter, Lactobacillus plantarum DAD-13, metformin, nonalcoholic fatty liver disease, visceral adipose tissue

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, dyslipidemia, and visceral adipose tissue dysfunction. Metformin and Lactobacillus plantarum DAD-13 may act through complementary metabolic and gut-microbiota pathways, but evidence on their combined administration is limited.

Objective: To evaluate the effects of combined metformin and L. plantarum DAD-13 administration on the Lee index, lipid profile, and visceral adipocyte number and diameter in a rat model of NAFLD.

Methods: Eighteen male Wistar rats (n = 6 per group) were allocated to a normal-diet group (ND), Western-diet group (WD), or Western-diet plus metformin-probiotic group (MP) for 28 weeks. During the final 10 weeks, the MP group received metformin at 50 mg/kg body weight/day and L. plantarum DAD-13 at 1 × 109 colonyforming units/mL, 1 mL/day. Lee index, serum lipid profile, and visceral adipose tissue histopathology were examined. Variable-specific parametric or nonparametric tests were used for analysis.

Results: Adipocyte diameter differed among groups (P = 0.007). The MP group had a lower mean adipocyte diameter than the WD group (64.8 vs. 72.8 μm; exploratory unadjustedP = 0.048). The adipocyte count was similar in both WD and MP groups (P = 0.655). Triglycerides differed among groups (P = 0.013) but the difference between the WD and MP groups was not significant (P = 0.130). No significant differences between groups were observed for the Lee index (P = 0.226), high-density lipoprotein cholesterol (P = 0.159), low-density lipoprotein cholesterol (P = 0.389), or total cholesterol (P = 0.785).

Conclusion: Combined metformin and L. plantarum DAD-13 administration was associated with a modest reduction in visceral adipocyte diameter compared with WD alone, but did not improve adipocyte count, Lee index, or most lipid outcomes. These exploratory findings do not establish synergism or a broad metabolic benefit.

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