Miso, fermented soybean paste, suppresses high-fat/high-sucrose diet-induced muscle atrophy in mice.

This study investigated the effects of miso, a traditional fermented soybean food in Japan, on muscle mass atrophy. Eight week old male C57BL/6J mice were fed high fat/high sucrose diet with or without miso for 12 weeks. A miso diet increased soleus muscle weights (p<0.05) and reduced intraperitoneal glucose tolerance and insulin tolerance (p<0.05). The miso diet downregulated the Tnfα and Ccl2 expression, related to inflammation, and Trim63 and Fbxo32 expression, related to muscle atrophy, in the soleus muscle (p<0.05). The miso diet increased short-chain fatty acids levels, including acetic, propanoic, and butanoic acids, in the feces, serum, and soleus muscle (p<0.05). According to the LEfSe analysis, the miso diet increased family Prevotellaceae, family Christensenellaceae, family Dehalobacterium, family Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales, whereas the miso diet decreased family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae. Miso suppressed high fat/high sucrose diet induced impaired glucose tolerance, low muscle strength, and muscle atrophy by improving dysbiosis and increasing short-chain fatty acids production and provides new insights into the preventive effects of fermented foods on sarcopenia.

Brazilian green propolis improves gut microbiota dysbiosis and protects against sarcopenic obesity.

INTRODUCTION: Brazilian green propolis is an important honeybee product that is considered beneficial for health. Here, we examined the therapeutic potential of dietary supplementation with propolis against sarcopenic obesity using Db/Db mice. METHODS: Db/m mice fed a normal diet alone and Db/Db mice fed normal diet alone, or supplemented with different amounts of propolis (0.08, 0.4 and 2%), were examined for effects on sarcopenic obesity. RESULTS: Propolis improved the glucose tolerance (P < 0.001), increased the grip strength (P < 0.001) and the weight of soleus (P = 0.006) and plantaris muscles (P = 0.008). Moreover, propolis improved the non-alcoholic fatty liver disease activity score (P < 0.001) and decreased the expression of genes related to inflammation, liver fibrosis and fatty acid metabolism. Propolis decreased the accumulation of saturated fatty acids in the liver and increased their excretion in faeces. With regard to the innate immunity, propolis decreased the ratio of M1 macrophages (P = 0.008) and Type 1 and 3 innate lymphoid cells to CD45-positive cells (P < 0.001) and increased the ratio of M2 macrophages (P = 0.002) and ILC2s (P = 0.007) in the liver. Additionally, propolis decreased the expression of genes related to muscle atrophy and inflammation and the concentration of saturated fatty acids in the soleus muscle. 16S rRNA phylogenetic sequencing revealed that propolis increased the Bacteroidetes/Firmicutes ratio, and the abundance of Butyricicoccus and Acetivibrio genera. Gut microbiota related to the pentose phosphatase pathway and glycerolipid metabolism was more prevalent after the administration of propolis. CONCLUSIONS: This is the first study to demonstrate that propolis can improve sarcopenic obesity by improving dysbiosis due to overeating and provides new insights into diet-microbiota interactions during sarcopenic obesity.

Gut Microbiota Changes by an SGLT2 Inhibitor, Luseogliflozin, Alters Metabolites Compared with Those in a Low Carbohydrate Diet in db/db Mice.

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.

Extracellular lipidome change by an SGLT2 inhibitor, luseogliflozin, contributes to prevent skeletal muscle atrophy in db/db mice.

BACKGROUND: Diabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy. METHODS: Eight-week-old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed. RESULTS: Administration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy-associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration. CONCLUSIONS: Intramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.

Impact of extracellular-to-intracellular fluid volume ratio on albuminuria in patients with type 2 diabetes: A cross-sectional and longitudinal cohort study.

AIMS/INTRODUCTION: Body fluid volume imbalance is common in patients with kidney failure, and is associated with all-cause mortality. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes mellitus without kidney failure. MATERIALS AND METHODS: Using data from one cohort study, a baseline cross-sectional study of 432 participants and a longitudinal cohort study of 368 participants who could follow up was carried out. Body fluid imbalance was determined by measuring the extracellular water (ECW)-to-intracellular water (ICW) ratio (ECW/ICW) using bioelectrical impedance analysis. A change in the urinary albumin-to-creatinine ratio (ACR) was defined as the ratio of urinary ACR at follow up to that at baseline. The ECW/ICW ratio was compared with the level of albuminuria. RESULTS: In this cross-sectional study, the ECW/ICW ratio increased with the level of albuminuria. There was an association between the ECW/ICW ratio and logarithms of urinary ACR after adjusting for covariates (ß = 0.205, P < 0.001). Furthermore, the ECW/ICW ratio was associated with a change in the urinary ACR after adjusting for covariates (ß = 0.176, P = 0.004) in this longitudinal study. According to the receiver operating characteristic curve, the optimal cut-off point of the ECW/ICW ratio for incident macroalbuminuria, defined as ACR >300 mg/gCr, was 0.648 (area under the curve 0.78, 95% confidence interval 0.58-0.90). CONCLUSIONS: The ECW/ICW ratio is independently associated with the level of albuminuria in patients with type 2 diabetes mellitus without kidney failure. This reinforces the importance of monitoring fluid balance in patients with type 2 diabetes mellitus.

Immune modulating effects of additional supplementation of estradiol combined with testosterone in murine testosterone-deficient NAFLD model.

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.

The Visceral Adiposity Index Is a Predictor of Incident Chronic Kidney Disease: A Population-Based Longitudinal Study.

BACKGROUND AND AIMS: Visceral adiposity index (VAI), calculated with body mass index, high density lipoprotein-cholesterol, triglycerides and waist circumference, has been proposed as a marker of visceral fat accumulation and dysfunction in adipose tissue. METHODS: The impact of VAI on incident chronic kidney disease (CKD) in a historical cohort study of 15,159 (8,260 men and 6,899 women) participants was investigated. CKD was defined when estimated glomerular filtration rate was <60 mL/min/1.73 m2 or proteinuria (positive: ≥1+). We divided the participants into 2 groups according to sex and into quartiles according to VAI (Q1-4). We performed Cox proportional hazard models, adjusting for age, smoking status, exercise, alcohol consumption, systolic blood pressure, hemoglobin A1c, uric acid, and creatinine. RESULTS: During the median 3.3-year follow-up for men and 3.2-year follow-up for women, 1,078 participants (629 men and 449 women) developed CKD. The 4,000 days cumulative incidence rate of CKD for men and women were 3.7 and 3.9% in Q1, 5.2 and 5.9% in Q2, 6.5 and 7.0% in Q3, and 8.4 and 9.3% in Q4 respectively. Compared to Q1, the hazard ratios of incident CKD in Q2, Q3 and Q4 for men and women were 1.23 (95% CI 0.91-1.66, p = 0.184) and 1.30 (0.87-1.96, p = 0.203), 1.42 (1.06-1.90, p = 0.018) and 1.38 (0.94-2.05, p = 0.105), and 1.51 (1.12-2.02, p = 0.006) and 1.65 (1.12-2.46, p = 0.013) respectively. Additionally, the area under the curve of VAI for incidence of CKD was superior to that of VAI in men (0.595 vs. 0.552, p < 0.001) and equal to in women (0.597 vs. 0.591, p = 0.708). CONCLUSIONS: The VAI can be a predictor of incident CKD.