Lipid-Modulating Effects of Sargassum fulvellum Fermented by Lactococcus lactis KCCM12759P and Leuconostoc mesenteroides KCCM12756P in Ovariectomized Mice

Abstract

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels-total cholesterol, triglycerides, LDL-C, and HDL-C-were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications.

Keywords: Sargassum; dyslipidemias; estrogen; fermentation; vitamin K2.

Figure 1

Sample preparation and experimental timeline for this in vivo study using Sargassum fulvellum (Sf). (a) Flowchart illustrating the feed preparation process using Sf and its fermented form (Sf_LlLm); (b) Schematic overview of the animal experiment involving sham-operated (CONT) and ovariectomized (OVX) C57BL/6 mice. Mice were assigned to the following groups (n = 5 per group): CONT, sham-operated mice fed a standard AIN-76A diet; nCONT, OVX mice fed the AIN-76A diet; pCONT, OVX mice fed AIN-76A supplemented with 17β-estradiol; Sf, OVX mice fed AIN-76A containing 10% Sf; and SfLlLm, OVX mice fed AIN-76A containing 10% SfLlLm. All treatments were administered for 8 weeks following a 2-week recovery period after sham or OVX surgery.

Figure 2

Effects of Sargassum fulvellum (Sf) and its fermented form (SfLlLm) on body, liver, and fat weights in ovariectomized (OVX) mice. (a) Representative dorsal images of mice from each group after 8 weeks of dietary intervention. (b) Final body weight (bar graph) and weight gain (line graph) in mice. (c) Relative liver weight normalized to body weight. (d) Relative fat weight, including epididymal and retroperitoneal fat, normalized to body weight. Data are presented as mean ± standard error of the mean (n = 5). # p < 0.05 vs. CONT (sham-operated control); * p < 0.05 vs. nCONT (OVX control), indicating significant effects of 17β-estradiol, Sf, or SfLlLm treatment.

Figure 3

Effects of Sargassum fulvellum (Sf) and its fermented form (SfLlLm) on hepatic lipid accumulation and serum biochemical parameters in ovariectomized (OVX) mice. (a) Serum alanine aminotransferase (ALT) levels. (b) Serum aspartate aminotransferase (AST) levels. (c) Representative histological images of liver tissues stained with hematoxylin and eosin (H&E), showing lipid accumulation in each group (scale bar = 100 µm). Data are expressed as mean ± standard error of the mean (n = 5). # p < 0.05 vs. CONT (sham-operated control); * p < 0.05 vs. nCONT (OVX control), indicating significant effects of 17β-estradiol, Sf, or SfLlLm treatment.

Figure 4

Effects of Sargassum fulvellum (Sf) and its fermented form (SfLlLm) on serum lipid levels and adipocyte morphology in ovariectomized (OVX) mice. (a) Serum total cholesterol (TC) levels. (b) Serum triglyceride (TG) levels. (c) Serum low-density lipoprotein cholesterol (LDL-C) levels. (d) Serum high-density lipoprotein cholesterol (HDL-C) levels. (e) Representative histological images of epididymal adipose tissue stained with hematoxylin and eosin (H&E), showing adipocyte size and distribution (scale bar = 100 µm). Data are presented as mean ± standard error of the mean (n = 5). # p < 0.05 vs. CONT (sham-operated control); * p < 0.05 vs. nCONT (OVX control), indicating significant effects of 17β-estradiol, Sf, or SfLlLm treatment.