Intermittent Fasting Sustainably Improves Glucose Tolerance in Normal Weight Male Mice Through Histone Hyperacetylation.

To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), followed by 4 weeks of ad libitum feeding, focusing on expression of genes for lipid metabolism in the skeletal muscle and histone acetylation in the promoter region. The 72hIF regimen resulted in metabolic remodeling, characterized by enhanced lipid utilization and mitochondrial activation in the muscle. This long-term IF (72hIF) caused stronger metabolic effects than alternate day fasting (24hIF) wherein fasting and refeeding are repeated every 24 hours. Upregulation of lipid oxidation genes and an increase in oxygen utilization were sustained even at 4 weeks after discontinuation of 72hIF, associated with histone hyperacetylation of the promoter region of uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) genes. An increase in leucine owing to fasting-induced muscle degradation was suggested to lead to the histone acetylation. These findings support the previously unappreciated notion that sustainable promotion of histone acetylation in lipid oxidation genes of the muscle and adipose tissues during and after IF may contribute to sustained metabolic effects of IF.

Activation of the intestinal tissue renin-angiotensin system by transient sodium loading in salt-sensitive rats.

BACKGROUND: The renal tissue renin-angiotensin system is known to be activated by salt loading in salt-sensitive rats; however, the response in other organs remains unclear. METHOD: Spontaneously hypertensive rats were subjected to normal tap water or transient high-salt-concentration water from 6 to 14 weeks of age and were thereafter given normal tap water. From 18 to 20 weeks of age, rats given water with a high salt concentration were treated with an angiotensin II type 1 receptor blocker, valsartan. RESULTS: Sustained blood pressure elevation by transient salt loading coincided with a persistent decrease in the fecal sodium content and sustained excess of the circulating volume in spontaneously hypertensive rats. Administration of valsartan sustainably reduced the blood pressure and normalized the fecal sodium levels. Notably, transient salt loading persistently induced the intestinal tissue renin-angiotensin system and enhanced sodium transporter expression exclusively in the small intestine of salt-sensitive rats, suggesting the potential connection of intestinal sodium absorption to salt sensitivity. CONCLUSION: These results reveal the previously unappreciated contribution of the intestinal tissue renin-angiotensin system to sodium homeostasis and blood pressure regulation in the pathophysiology of salt-sensitive hypertension.

Mediastinal Cystic Parathyroid Adenoma Diagnosed by Somatostatin Receptor Scintigraphy.

A 71-year-old man complained of nausea and loss of appetite for eight months prior to admission. He was transported to a hospital with disorientation and diagnosed with primary hyperparathyroidism by laboratory examinations. However, ultrasonography, computed tomography, and technetium-99m labeled methoxyisobutyl isonitrile (99mTc-MIBI) with single-photon emission computed tomography did not yield definite results. In contrast, somatostatin receptor scintigraphy successfully identified the lesion responsible for the over-secretion of parathyroid hormone within the middle mediastinum. The tumor was successfully resected by surgery, and a histopathological analysis confirmed the parathyroid adenoma nature of the tumor.

Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial.

BACKGROUND: The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home-based exercise programme on physical functioning and health-related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15-30 mL/min/1.73 m2 . METHODS: Forty-six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40-60% peak heart rate thrice weekly and resistance training at 70% of one-repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life-Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD. RESULTS: Improvement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. -21.3 ± 46.1; P < 0.001). Among Kidney Disease Quality of Life domains, significant mean differences were observed between the exercise group and the control group in work status, quality of social interaction, and kidney disease component summary outcomes (12.76 ± 5.76, P = 0.03; 5.97 ± 2.59, P = 0.03; and 4.81 ± 1.71, P = 0.007, respectively). There were greater reductions in natural log (ln)-transformed urinary excretion of liver-type fatty acid-binding protein, ln serum C-reactive protein, and acylcarnitine to free carnitine ratio in the exercise group compared with controls, with significant between-group differences of -0.579 ± 0.217 (P = 0.008), -1.13 ± 0.35 (P = 0.003), and -0. 058 ± 0.024 (P = 0.01), respectively. CONCLUSIONS: Our 6 month home-based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD-related parameters.