Heat-killed Lactiplantibacillus plantarum Shinshu N-07 exerts antiobesity effects in western diet-induced obese mice.

AIMS: The aim of this study was to evaluate the antiobesity effects of heat-killed Lactiplantibacillus plantarum Shinshu N-07 (N-07) isolated from fermented Brassica rapa L. METHODS AND RESULTS: Male mice were divided into three groups (n = 10/group); normal diet, western diet (WD), or WD + N-07 (N-07) group and administered each diet for 56 days. The N-07 group showed significant suppression of body weight gain and epididymal fat, perirenal fat, and liver weights compared with the WD group. Higher levels of fecal total cholesterol, triglyceride (TG), and free fatty acid (FFA) were observed in the N-07 group than in the WD group. The mRNA expression of the cholesterol transporter ATP-binding cassette transporter G5 (ABCG5) was significantly increased in the small intestine of N-07-fed mice compared with WD-fed mice. Moreover, N-07 supplementation significantly increased the mRNA expression of ABCG5 and ABCG8 in Caco-2 cells. Furthermore, the TG- and FFA-removal ability of N-07 was confirmed to evaluate its soybean oil- and oleic acid-binding capacities in in vitro experiments. CONCLUSIONS: The antiobesity effects of N-07 might be due to its ability to promote lipid excretion by regulating cholesterol transporter expression and lipid-binding ability.

Brassica rapa L. prevents Western diet-induced obesity in C57BL/6 mice through its binding capacity of cholesterol and fat.

Obesity, a chronic disorder caused by excessive energy intake leading to fat accumulation in adipose tissue, increases the risk of severe diseases. Brassica rapa L. is known as a traditional vegetable in the Nagano area of Japan. C57BL/6 mice were randomly assigned to three groups, with different diets as follows: a normal diet, a Western diet (WD), and a WD plus B. rapa L. powder (BP) in a 56-day experiment. Brassica rapa L. supplementation reduced the body weight gain and lipid accumulation of mice significantly. The BP group also had higher fecal bile acid, total cholesterol, and triglyceride excretion levels compared with those in the other groups. The antiobesity effects of B. rapa L. were due to its binding with cholesterol and fat, and possibly enhancing the bile acid excretion and modulating gut microbiota, suggesting that B. rapa L. could be a functional vegetable with potential uses in targeting obesity.

Procyanidin B2 gallate regulates TNF-α production from T cells through inhibiting glycolytic activity via mTOR-HIF-1 pathway.

Procyanidins are polyphenols with antioxidant, anti-obesity, and anti-inflammatory properties. Procyanidin B2 (PCB2) gallate; specifically, PCB2 3,3″-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the molecular interactions and partners of PCB2DG underlying this suppression of cytokine production are unclear. The present study aimed to elucidate mechanisms underlying regulation of tumor necrosis factor (TNF)-α production by PCB2DG. We found that production of TNF-α and glycolytic activity in activated CD4+ T cells were suppressed by PCB2DG treatment. The inhibition of TNF-α production was found to be mediated by mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1 (HIF-1) pathway, as PCB2DG suppressed the expression of HIF-1α, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). Moreover, suppression of TNF-α production was mediated by regulation of the glycolytic enzyme lactate dehydrogenase at the posttranscriptional level. These results suggest that PCB2DG regulates TNF-α production by inhibiting glycolytic activity via the mTOR-HIF-1 pathway.

MicroRNA 16-5p is upregulated in calorie-restricted mice and modulates inflammatory cytokines of macrophages.

Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decrease mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. However, the detailed mechanisms of immunomodulation by CR remain unclear. In this study, we established a mouse model for CR and analyzed the changes of immune cells in these mice. The CR mice fed a calorie-restricted diet for 4 weeks had lower body weight and fat mass compared with control mice. The proportions of CD4+, CD8+, and naïve CD4+ T cells in spleen cells from CR mice were higher than those in of control mice. Additionally, the proportion of CD8+ T cells was significantly decreased and the mRNA expression of proinflammatory cytokines in the colon of CR mice was significantly decreased compared with those of control mice. To determine the effect of CR on microRNA (miRNA) expression, serum and tissues were collected from mice and the expression level of miRNA was analyzed by real-time RT-PCR. As a result, the expressions of miR-16-5p, miR-196b-5p, and miR-218-5p in serum from CR mice were higher than those in control mice. The expression of miR-16-5p increased in the spleen, thymus, colon, and stomach of CR mice compared with expression in control mice. Furthermore, RAW264 cells transfected with a miR-16-5p mimic significantly decreased the mRNA expression of IL-1ß, IL-6, and TNF-α under LPS stimulation. These results suggested that miR-16-5p might be a critical factor involving the anti-inflammatory effects of calorie-restricted feeding.