17beta-estradiol supplementation decreases glucose rate of appearance and disappearance with no effect on glycogen utilization during moderate intensity exercise in men

CONTEXT AND OBJECTIVE: Women use less carbohydrate during endurance exercise, as compared with men. In rodents, 17beta-estradiol (E2) supplementation robustly increases lipid use and lowers muscle and liver glycogen use during exercise. E2 supplementation has been found to influence substrate selection by decreasing glucose rate of appearance (Ra), disappearance (Rd), and metabolic clearance rate during exercise in humans; however, neither a change in total carbohydrate use nor a sparing of muscle glycogen was demonstrated. SUBJECTS AND METHODS: We investigated the effect of 8 d of E2 (2 mg/d) supplementation on glucose turnover and net muscle glycogen use in 11 men using a randomized, double-blind, placebo-controlled, crossover design. Subjects underwent primed constant infusion of [6,6-(2)H]glucose, and muscle biopsies were taken before and after 90 min of cycling at 65% maximal oxygen uptake. RESULTS: E2 supplementation decreased the respiratory exchange ratio (P = 0.03) and glucose Ra and Rd (both P = 0.04) during exercise, as compared with placebo. E2 supplementation lowered proglycogen (P < 0.05) and total glycogen (P = 0.04) concentration, as compared with placebo; however, there was no effect of E2 on net muscle glycogen use during exercise. CONCLUSIONS: These findings show that E2 supplementation alters fuel selection in exercising men by increasing lipid use and reducing carbohydrate use, glucose Ra (primarily liver glucose production), and Rd (primarily muscle glucose uptake). Furthermore, E2 reduces the basal level of total muscle glycogen, particularly the proglycogen form.     

Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.     

Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training

Proteins that coat the lipid droplets (also known as PAT proteins or perilipin (PLIN) family proteins) have diverse functions that are not well elucidated in many tissues. In skeletal muscle, there is even less known about the functions or characteristics of these proteins or how they might change in response to perturbations that alter both intramyocellular lipid (IMCL) content and fat utilization and oxidation. Therefore, the purpose of this study was to examine the human muscle content and gene expression of the four skeletal muscle PLIN proteins in both lean and obese men and women and how this was changed following a 12-week endurance training protocol. PLIN2-PLIN5 proteins were all more abundant in women than in men (p?= 0.037 and?p?< 0.0001, respectively), consistent with higher IMCL content observed in female skeletal muscle. PLIN5 (previously known as OXPAT) is of particular interest because it has previously been associated primarily with oxidative tissues that rely heavily on fat oxidation for energy production. Although PLIN5 was not different between lean and obese subjects, it was the only PLIN protein to increase in response to endurance training in both sexes. PLIN5 correlated with IMCL volume (p?< 0.0001), but in general, the other PLIN proteins did not correlate well with IMCL volume, suggesting that the relationship between lipid accumulation and PLIN family protein content is not a simple one. Although more work is necessary, it is clear that PLIN5 likely plays an important role in IMCL accumulation and oxidation, both of which increase with endurance training in human skeletal muscle.     

Diets to Prevent Coronary Heart Disease 1957-2013: What Have We Learned?

Our understanding of the potential cardioprotective properties of nutrition is relatively recent, with most relevant studies completed in the last several decades. During that time, there has been an evolution in the focus of nutritional intervention. Early trials emphasized reduction of dietary fat with the goal of preventing heart disease by reducing serum cholesterol. Results from trials focused exclusively on dietary fat reduction were disappointing, prompting subsequent studies incorporating a whole diet approach with a nuanced recommendation for fat intake. The Mediterranean-style diet, with a focus on vegetables, fruit, fish, whole grains, and olive oil, has proven to reduce cardiovascular events to a degree greater than low-fat diets and equal to or greater than the benefit observed in statin trials.     

Studies on the hypoglycemic effects of Murraya paniculata Linn. extract on alloxan-induced oxidative stress in diabetic and non-diabetic models

ObjectiveTo evaluate the effect of extract of Murraya paniculata Linn. (Family – Rutaceae) on blood glucose, cholesterol, triglyceride and lipid level and antioxidant status in alloxan induced diabetic and non-diabetic rats.MethodsHydro-alcoholic extract of M. paniculata leaves (100, 200 and 400 mg/kg) was administered orally for 14 days and its effect on blood glucose, cholesterol, triglycerides and lipid level were estimated in serum. Liver free radical (lipid peroxidation, LPO) and antioxidant (Super oxide dismutase, SOD; catalase, CAT; and reduced glutathione peroxidase, GPx) were also measured after 14 days treatment with extract. Glucose level in non-diabetic rats was estimated after 21 days treatment with M. paniculata extract.ResultsOral administrations of M. paniculata extract (100, 200 and 400 mg/kg) for 14 days significantly reduced the levels of blood glucose, cholesterol, and triglyceride and lipid level. Liver free radical (LPO) significantly reduced and antioxidants (SOD, CAT and GPx) status significantly increase after 14 days treatment of extract in diabetic rats. M. paniculata 200 and 400 mg/kg significantly decrease glucose level in non-diabetic rats after 21 day and caused hypoglycemia in normal rats.ConclusionsM. paniculata leaves extract posses hypoglycemic effect in oxidative stress condition and also in non-diabetic condition. Hypoglycemic action may be by potentiating of the insulin effect by increasing either the pancreatic secretion of insulin from beta cells of islets of langerhans or its release from the bound form. M. paniculata could be a potential source of hypoglycemic agent with antioxidant properties.     

Kupffer cell erythrophagocytosis and graft-versus-host hemolysis in liver transplantation

BACKGROUND & AIMS: Graft-versus-host hemolysis (GVHH) syndrome develops in approximately half of patients undergoing ABO-unmatched liver transplantation. The clinical and laboratory presentations of GVHH syndrome often mimic acute rejection, leading to liver biopsy for definitive diagnosis. The purpose of this study was to investigate if there are specific histological findings that permit diagnosis of GVHH syndrome and to assess the relationship between GVHH syndrome and rejection. METHODS: Clinical and laboratory evidence of GVHH syndrome, results of liver biopsy, and clinical outcome were assessed in 30 ABO- unmatched liver transplant recipients. Biopsy results were compared with those of two control groups consisting of patients who had normal liver test findings (protocol biopsy) and rejection. RESULTS: Sixteen of the 30 patients (53%) had evidence of GVHH syndrome. Erythrophagocytosis was noted in each biopsy specimen, and the degree of phagocytosis correlated significantly with the amount of blood given after postoperative day 5 (r = 0.9; P < 0.02). Electron-microscopic studies performed randomly in 5 patients showed that the red cells were located in Kupffer cells. In contrast, erythrophagocytosis was minimal in the two control groups. Despite an incidence and severity of rejection similar to those in other liver transplant patients, serum transaminase levels were significantly higher in patients with GVHH syndrome. CONCLUSIONS: Erythrophagocytosis is a sensitive histological marker of GVHH syndrome. The severity of rejection and response to antirejection therapy should be monitored by markers other than transaminases in patients with GVHH syndrome. (Gastroenterology 1996 Jun;110(6):1891-6)