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Background: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD)., Methods: At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed., Results: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones., Conclusions: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women., Competing Interests: Nakajima, H. received individual compensation from Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Nakanishi, N. received individual compensation from Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., and TERUMO CORPORATION. Hamaguchi, M. received grants from AstraZeneca K.K., Ono Pharma Co., Ltd., and Kowa Pharmaceutical Co., Ltd.; and also received individual compensation from AstraZeneca K.K., Ono Pharma Co., Ltd., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., and Kowa Pharmaceutical Co., Ltd. outside of the submitted work. Fukui, M. received grants from Ono Pharma Co., Ltd., Oishi Kenko Inc., Yamada Bee Farm, Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Eli Lilly Japan K.K., Taisho Pharmaceutical Co., Ltd., Terumo Corp., Teijin Pharma Ltd., Nippon Chemiphar Co., Ltd., Abbott Japan Co., Ltd., and Johnson & Johnson K.K. Medical Co., TERUMO CORPORATION, and also received individual compensation from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Eli Lilly Japan K.K., Taisho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Teijin Pharma Ltd., Arkray Inc., Medtronic Japan Co., Ltd., and Nipro Corp., TERUMO CORPORATION, outside of the submitted work. Sasano, R. was employed by the company AiSTI SCIENCE Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Royal jelly (RJ) is a naturally occurring substance synthesized by honeybees and has various health benefits. Herein, we focused on the medium-chain fatty acids (MCFAs) unique to RJ and evaluated their therapeutic efficacy in treating non-alcoholic fatty liver disease (NAFLD). We examined db / m mice that were exclusively fed a normal diet, db / db mice exclusively fed a normal diet, and db / db mice fed varying RJ quantities (0.2, 1, and 5%). RJ improved NAFLD activity scores and decreased gene expression related to fatty acid metabolism, fibrosis, and inflammation in the liver. RJ regulated innate immunity-related inflammatory responses in the small intestine and decreased the expression of genes associated with inflammation and nutrient absorption transporters. RJ increased the number of operational taxonomic units, the abundance of Bacteroides , and seven taxa, including bacteria that produce short-chain fatty acids. RJ increased the concentrations of RJ-related MCFAs (10-hidroxy-2-decenoic acid, 10-hydroxydecanoic acid, 2-decenedioic acid, and sebacic acid) in the serum and liver. These RJ-related MCFAs decreased saturated fatty acid deposition in HepG2 cells and decreased the gene expression associated with fibrosis and fatty acid metabolism. RJ and RJ-related MCFAs improved dysbiosis and regulated the expression of inflammation-, fibrosis-, and nutrient absorption transporter-related genes, thereby preventing NAFLD.

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w / w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria , Enterobacteriaceae , Escherichia , Enterobacterales , and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus , Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis , and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber derived through controlled enzymatic hydrolysis of guar gum, a highly viscous galactomannan derived from the seeds of Cyamopsis tetragonoloba . Here, we examined the therapeutic potential of dietary supplementation with PHGG against sarcopenic obesity using Db/Db mice. Db/Db mice fed a normal diet alone or a fiber-free diet, or supplemented with a diet containing PHGG (5%), were examined. PHGG increased grip strength and the weight of skeletal muscles. PHGG increased the short-chain fatty acids (SCFAs) concentration in feces and sera. Concerning innate immunity, PHGG decreased the ratio of inflammatory cells, while increasing the ratio of anti-inflammatory cells in the small intestine. The present study demonstrated the preventive effect of PHGG on sarcopenic obesity. Changes in nutrient absorption might be involved through the promotion of an anti-inflammatory shift of innate immunity in the intestine accompanied by an increase in SCFA production by PHGG.