Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome.

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.

Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans.

BACKGROUND: Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate. OBJECTIVE: We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition. METHODS: We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution. RESULTS: Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group. CONCLUSIONS: These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.

Epigallocatechin-3-gallate alleviates bladder overactivity in a rat model with metabolic syndrome and ovarian hormone deficiency through mitochondria apoptosis pathways.

Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound in green tea, has been shown to protect against ovarian hormone deficiency induced overactive bladder (OAB). The present study investigated oxidative stress induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism underlying the protective effect of EGCG (10 umol/kg/day) on bladder overactivity. Rats were fed with high fat high sugar (HFHS) diet to induce MetS and received ovariectomy surgery to deprive ovarian hormone. By dieting with HFHS for 6 months, rats developed MetS and OAB. MetS + OVX deteriorated bladder storage dysfunction more profound than MetS alone. MetS and MetS + OVX rats showed over-expression of inflammatory and fibrosis markers (1.7~3.8-fold of control). EGCG pretreatment alleviated storage dysfunction, and protected the bladders from MetS and OVX - induced interstitial fibrosis changes. Moreover, OVX exacerbated MetS related bladder apoptosis (2.3~4.5-fold of control; 1.8~2.6-fold of Mets group), enhances oxidative stress markers (3.6~4.3-fold of control; 1.8~2.2-fold of Mets group) and mitochondrial enzyme complexes subunits (1.8~3.7-fold of control; 1.5~3.4-fold of Mets group). EGCG pretreatment alleviated bladder apoptosis, attenuated oxidative stress, and reduced the mitochondrial and endoplasmic reticulum apoptotic signals. In conclusions, HFHS feeding and ovarian hormone deficiency enhances the generation of oxidative stress mediated through mitochondrial pathway. EGCG reduced the generation of oxidative stress and lessened bladder overactivity.

Muscle Carnosine Concentration with the Co-Ingestion of Carbohydrate with ß-alanine in Male Rats.

Muscle carnosine is an intracellular buffer. The intake of ß-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by ß-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: ß-alanine (ßA group, 1.8% ß-alanine in drinking water), ß-alanine and glucose (ßAGL group, 1.8% ß-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, rats were exercised (20 m·min-1, 10 min·day-1, 4 days·week-1 for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, ßA, and ßAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, ßA, and ßAGL respectively. In each muscle, ßA and ßAGL resulted in similar carnosine increases compared to the control. In conclusion, ß-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.