Although there was no difference in food and energy intake between the HSD group and BNR17 groups ( and ), the increase in body weight was suppressed in the BNR17 groups ( and ). There was a significant reduction in subcutaneous and abdominal fat mass in BNR17-fed groups compared to the HSD group (). Subcutaneous fat and abdominal fat are the major types of white adipose tissue. Abdominal obesity is associated with increased risk of insulin resistance and cardiovascular diseases, whereas increased subcutaneous fat correlates with a favorable plasma lipid profile 
. Indeed, the mean adipocyte sizes of all white adipose tissues were remarkably reduced in BNR17-fed mice (). Subcutaneous adipocytes are the main source of leptin and adiponectin 
. Leptin is an adipocyte hormone that controls body weight by regulating food intake and energy expenditure 
. Leptin concentrations are correlated with the percentage of body fat; higher serum levels have been found in obese individuals compared with non-obese individuals 
. BNR17 suppressed the elevation of plasma leptin (), suggesting that the reductions in fat mass and body weight are associated with a reduction in leptin. Similar effects have been observed in other studies 
. For the liver, the weight reduction were observed in BNR17 groups (), however HE staining and O-red staining of liver tissue did not show any changes between groups (Data not shown).
In this study, glucose was not change between groups. In the paper that investigated the role of fatty acid composition in the development of metabolic disorders in sucrose-induced obese rates, the different time courses of the increases in plasma glucose, insulin, and triglycerides during the course of developing obesity suggest that some time- or tissue-dependent process is necessary to induce these metabolic abnormalities 
Some studies have reported that the feeding of a low-protein, high-carbohydrate diet (6% protein and 74% carbohydrate) induced an increase in lipid content in the whole carcass, epididymal adipose tissue and retroperitoneal adipose tissue 
. Long-term (16 weeks) feeding of a high-sucrose (65%) diet to C57BL/6 mice induced obesity, hepatic steatosis, and insulin resistance 
. In Asian populations, including Koreans, Chinese and Japanese, the traditional diet is characterized as being high in carbohydrate rather than fat, thus the increasing prevalence of obesity is associated with a high carbohydrate intake. Among Korean adults, a high carbohydrate intake is inversely associated with HDL-cholesterol 
. In the current study, significant increases in body weight and fat mass in HSD groups were induced for 10 weeks as compared to the normal diet ( and ), and increases in lipid profile (total cholesterol, LDL- and HDL-cholesterol) were induced by high-sucrose diet feeding.
Because obesity results from low energy expenditure and increased fatty acid synthesis, we measured the mRNA expression levels of related genes in liver and white adipose tissues. In the liver, the administration of BNR17 significantly increased mRNA expression of ACO, CPT1, ANGPTL4, PPARα and PPARδ, as compared to the HSD group (). ACO and CPT1 are considered to be rate-limiting enzymes in mitochondrial fatty acid oxidation 
and ANGPTL4 is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes 
. These genes are target genes of PPARs, which have essential roles in energy homeostasis and adipogenesis 
, and their expression is increased by the activation and elevation of PPARα and PPARδ, resulting in anti-obesity effects. Excess adipose tissue mass is caused mainly by the differentiation of precursor cells into new adipocytes (adipogenesis). Several transcription factors including CCAAT/enhancer binding protein-α (C/EBPα), PPARγ, SREBP-1c are involved in this process 
. PPARγ regulates the expression of adipocyte genes such as adipocyte-fatty acid binding protein (A-FABP) 
, and SREBP-1c controls the expression of lipogenic genes such as FAS and ACC 
. We observed tendencies for reduced SREBP-1c and ACC in the BNR17-fed groups compared to the HSD group; however, we did not detect a reduction in mRNA expression of FAS, the rate-limiting enzyme of fatty acid synthesis in the liver (). Moreover, PPARγ and LPL, which are related to fat intake, did not differ among the HSD group and BNR17-fed groups (). Therefore, it seems that the anti-obesity effect of BNR17 is responsible for the increased expression of fatty acid metabolism-related genes rather than reduced fatty acid synthesis and fat intake in the liver.
In this study, BNR17 did not show dose-dependent suppression of body weight and fat mass gain as there was no significant difference in biomarkers between the BNR17(9) and BNR17(10) groups. This suggests that BNR17 exhibits anti-obesity activity at doses >109
CFU. This is not consistent with a previous study of the dose-dependent anti-diabetic activity of BNR17 in db/db
. Although we did not clarify the reason in this study, recently, it has been reported that immunomodulation of dendritic cells by probiotics showed very different profiles according to the bacterial inoculum, so the probiotic effect may differ depending on the frequency and size of doses ingested 
. This means that the determination of the optimal effective dose of probiotics may be required for the future development of commercial products.
Interestingly, we observed changes in several diabetes-related biomarkers in this study. GLUT4 is one of the main glucose transporters expressed in skeletal muscle and adipose tissue. An increase in GLUT4 expression in skeletal muscle is known to ameliorate insulin resistance associated with obesity or diabetes 
, while it has been reported that adipose GLUT4 gene expression changes were more related to insulin resistance and type 2 diabetes rather than obesity 
. In our study, BNR17 significantly increased GLUT4 mRNA expression in white adipose tissue (). Furthermore, the insulin level increased in the HSD group, which was decreased significantly by BNR17 supplementation (). In the case of pre-diabetes, increases in blood glucose stimulate the secretion of insulin and subsequently induce hyperinsulinemia with a normal blood glucose range. Hyperinsulinemia is frequently accompanied by obesity, and a biomarker of insulin resistance 
. It is expected that the regulation of GLUT4 and insulin can likely be attributed to the anti-diabetes activity of BNR17.
Recently, many studies have reported the preventive activity of probiotic lactic acid bacteria on obesity and metabolic syndrome. L. plantarum
KY1032 cell extract reduced fat mass by modulating adipogenesis in maturing preadipocytes 
. L. paracasei
decreased fat storage by increasing the level of ANGPTL4 
. VSL no. 3, a mixture of bifidobacteria, lactobacilli and Streptococcus thermophilus
, improved diet-induced obesity, hepatic steatosis and insulin resistance by increasing hepatic natural killer T-cells and reducing inflammatory signaling in mice 
. On the other hand, it was reported recently that gut microbes play an important role in body weight regulation. Endogenous Bifidobacterium
spp. were significantly and positively correlated with improved glucose tolerance, glucose-induced insulin secretion and normalized inflammatory tone (decreased endotoxemia, plasma and adipose tissue proinflammatory cytokines) in high-fat-diet and prebiotic-treated mice 
. Whether supplementation with exogenous probiotic strains has the same mechanism of action is unclear 
. However, Lactobacillus
are main members of the gut microbiota, and therefore it is worthwhile to investigate the effect of probiotics on the relationship between the gut microbiota and obesity or obesity-related diseases. In summary, the probiotic L. gasseri
BNR17 lowered body weight and adiposity by increasing the expression of fatty-acid oxidation genes and reducing the levels of leptin and insulin in high-sucrose diet-induced obese mice. This suggests that L. gasseri
BNR17 may facilitate alleviating metabolic syndrome.