Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short-term starvation versus low-carbohydrate (CHO)/high-fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy (1H-MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water-only starvation (S); and (b) very low-CHO/high-fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross-over design. The level of dietary-induced IMTG accumulation (P = 0.46), insulin resistance (P = 0.27) and glucose intolerance (P = 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated (r = -0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.     

Unconditioned and conditioned effects of intravenous insulin and glucose on heart rate variability in healthy men

We examined whether an injection of intravenous insulin and intravenous glucose would affect frequency-domain measures of heart rate variability (HRV), i.e., the high-frequency (HF-) band and the ratio of the low frequency (LF-) to the HF-band in healthy humans. Using a classical conditioning protocol, we also assessed whether the measures of HRV are subject to classical conditioning. Thirty healthy men were divided into three groups, given a conditioned stimulus (CS) and an intravenous injection of either insulin (0.05 IU/kg) in Group 1, glucose (15%, 0.5 g/kg) in Group 2, or placebo (physiological saline [0.9%]) in Group 3 during the 4-day acquisition phase. All subjects were given an olfactory CS (rosewood-peppermint smell) and placebo injection on day 5 (test). Due to their high inter-individual variability, HF and LF/HF-ratio were analysed by intragroup comparisons, using a pre-injection baseline interval (min -15 to -5), and three functional post-injection intervals: a) the interval to the maximum insulin level, i. e. insulin peak (min 0-5) in Groups 1 and 2, b) the interval to the maximum of insulin-induced hypoglycaemia (min 20-25) in Group 1, and c) the end of the session (min 70-75). On days 1 to 4, we found significant increases of the HF-band from baseline to interval min 0-5 in Group 1, and an even more pronounced increase in the glucose-treated Group 2. At the test (Day 5), both experimental groups responded with an HF-increase in the interval of the former insulin peak, and also at the other measurement intervals, reflecting some general increase of vagal activity remaining as a conditioned response. On days 1 to 4, the HF-band was positively correlated with the change of peripheral insulin levels in Group 1, reaching statistical significance on days 3 and 4. This pattern only emerged in tendency on Day 4 in Group 2. In conclusion, insulin triggers an increase in parasympathetic tone at maximum hyperinsulinaemia, and our data support the notion that this response pattern can become classically conditioned.     

高脂环境对大鼠成肌细胞糖脂代谢的影响

目的: 探讨棕榈酸(PA)形成的高脂环境对大鼠成肌细胞糖代谢的影响,为深入研究2型糖尿病的发生机制提供理论依据。方法: 用0.1、0.3、0.5 mmol/L棕榈酸处理原代培养大鼠成肌细胞6、12、24 h后,用MTT法检测成肌细胞活力;用油红O染色法检测成肌细胞脂肪变性后甘油三酯沉积;用甘油磷酸氧化酶-过氧化物酶(GPO-POD)法测定成肌细胞脂肪变性后甘油三酯含量;用同位素示踪法检测葡萄糖摄取。结果: 随着PA处理浓度(0.1-0.5 mmol/L)的增加,及暴露时间(6~24 h)的增加,成肌细胞活力逐渐降低、甘油三酯沉积及含量不断增高、葡萄糖摄取不断降低,并呈现剂量和时间依赖性的效应关系。与对照组比较,0.3 mmol/L PA(24 h)和0.5 mmol/L PA(12、24 h)造成细胞活力、甘油三酯沉积及含量、葡萄糖摄取的改变最为明显。结论: PA可以作用于大鼠成肌细胞,使其脂肪沉积,甘油三酯含量增加,糖摄取减少,并呈剂量依赖关系。     

Effects of transcutaneous short-term electrical stimulation on M. vastus lateralis characteristics of healthy young men

Fifteen healthy, untrained male subjects (mean age +/- SD, 22 +/- 5 years) were used to examine the plasticity of myosin heavy chain phenotype, size, oxidative capacity and capillarization of skeletal muscle fibre types with short-term electrical stimulation (ES). Ten subjects were electro-stimulated on both quadriceps muscles with a frequency of 45-60 Hz, with 12 s of stimulation followed by 8 s of recovery for a total of 30 min per day, 3 days per week for 6 weeks. The remaining five subjects served as controls. Two vastus lateralis muscle biopsy samples were removed from each subject before (week 0) and after (week 6) ES training. A standardized exercise test on a cycle ergometer was performed by each subject before and after the experimental period and several indicators of whole-body aerobic capacity were estimated. The so-called electromyographic threshold was also determined during the tests. Muscle biopsy samples were analysed by electrophoresis, immunohistochemistry and quantitative histochemistry. Myosin heavy chain (MHC) composition, muscle fibre type distribution, fibre areas, oxidative capacity and capillaries of each fibre type were estimated. Muscular changes with ES revealed an increase of fibres expressing MHC-IIA, and a decrease of fibres expressing MHC-IIX and MHC-I, as well as an increase of the oxidative capacity and mean number of capillaries of fast-twitch (type II) fibres with minimal muscle fibre hypertrophy. These adaptations seem related to a bi-directional transformation from both MHC isoforms I and IIX towards the MHC-IIA isoform. The aerobic performance and electromyographic variables at the whole-body level were not altered by ES. These results indicate that the particular short-term ES training protocol tested in the present study induces significant adaptations in histochemical and metabolic machineries of human skeletal muscle. The results also offer new perspectives for realistic applications of ES in various clinical situations and sport training.     

Effects of short-term cholestyramine feeding on cholesterol metabolism in differently aged rats

The effects of short-term (7 days) feeding of a diet containing cholestyramine (5%) on the cholesterol metabolism were studied in male Sprague-Dawley rats at ages of 5 weeks (young) and 9-10 months (adult). Cholestyramine significantly enhanced the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase both in young and adult rats; however, the absolute values were significantly higher in the former. The time-courses of changes in the activities of these enzymes after cessation of cholestyramine were comparable in both groups of rats. The rate of incorporation of mevalonate into sterol was also higher in young than in adult rats, while the stimulating effect of cholestyramine was markedly greater in adult rats. Hepatic acyl-CoA:cholesterol acyltransferase activity was comparable, but cholestyramine significantly decreased it only in adult rats. In adult rats hepatic cholesterol was decreased significantly by the resin while it remained uninfluenced in young rats. The serum cholesterol level tended to be higher in adult rats regardless of the dietary manipulation. The results indicate an appreciable age-dependent change in the hepatic cholesterol metabolism in response to the interruption of enterohepatic circulation of bile acids.     

Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans

Pancreatic tissue obtained by hemipancreatectomy from healthy living related donors has been transplanted into recipients with Type I diabetes mellitus. To determine the metabolic consequences of this procedure for the donors, we carried out oral glucose-tolerance testing and 24-hour monitoring of serum glucose levels and urinary C-peptide excretion as a measure of insulin secretion in 28 donors, both before and one year after hemipancreatectomy. The mean fasting serum glucose level was significantly higher one year after the procedure (mean +/- SD, 5.4 +/- 0.9 vs. 4.9 +/- 0.5 mmol per liter; P less than 0.003), as was the serum glucose value two hours after the administration of glucose (8.7 +/- 2.9 vs. 6.5 +/- 1.0 mmol per liter; P less than 0.001). The fasting serum insulin level was significantly lower one year after hemipancreatectomy (33.0 +/- 21.6 vs. 38.4 +/- 21.6 pmol per liter; P less than 0.05), as was the area under the insulin curves during the oral glucose-tolerance test (52,554 +/- 22,320 vs. 76,230 +/- 33,354 pmol per liter per minute; P less than 0.04). The mean 24-hour serum glucose-profile value was higher at one year, and the 24-hour urinary C-peptide excretion was lower in the 17 donors who underwent these studies. Seven of the 28 donors had abnormal glucose tolerance one year after hemipancreatectomy; however, insulin secretion in these 7 donors was indistinguishable from that in the 21 donors who had normal glucose tolerance. All 28 donors had fasting serum glucose concentrations lower than 7.8 mmol per liter, and their mean 24-hour plasma glucose levels remained within the normal range. We conclude that in healthy donors hemipancreatectomy results in a deterioration of insulin secretion and glucose tolerance, as measured one year later. Further study is required to ascertain whether the development of clinical diabetes mellitus is a risk inherent in hemipancreatectomy.     

Deterioration of sperm quality in young healthy Belgian men

We have retrospectively analysed the sperm characteristics of416 consecutive healthy young men who presented themselves inthe past 19 years as candidate sperm donors. Ejaculate volumeincreased slightly (P = 0.067), and average sperm concentrationdecreased (P = 0.035) by 12.4xlO6ml over the observation period,so that sperm count per ejaculate remained unchanged (P = 0.91).In contrast, sperm morphology (r = –0.23, P < 0.0001),rapid progressive motility (r = –0.42, P < 0.0001)and total motility (r = –0.33, P < 0.0001) presentedan important and time-related decrease. When a quadratic modelwas used rather than a linear one to analyse the data on rapidprogressive motility, there appeared to have been no furtherdecline since 1990. The average proportion of spermatozoa withnormal morphology decreased from 39.2% in the period 1977–1980to 26.6% in 1990–1995 (P < 0.0001), and the mean percentageof spermatozoa with rapid progressive motility decreased from52.7 to 31.7% (P < 0.0001). The percentage of candidate donorswith sperm characteristics below the 5th percentile cut-offvalue of a normal fertile population increased from 13 to 54%during the observation period (P < 0.0001). Since the techniqueof semen analysis has remained essentially unchanged in-so-faras has been practically possible, as has the method of recruitmentof candidate sperm donors, the observed deterioration of spermcharacteristics is considered to reflect degeneration of spermproduction among men aged between 20 and 40 years.     

高脂饮食诱发血糖升高的动物模型中瘦素与胰岛素变化的关系

高脂饲料喂养大鼠,诱发胰岛素抵抗形成血糖升高,以研究瘦素与糖尿病的关系。将大鼠分为正常和高脂饲料喂养组,于喂养前及喂养30、60d时测血糖、瘦素与胰岛素水平,行高胰岛素正常血糖钳夹试验,最后分离分离脂肪称重。结果：高脂饮食组具有明显的胰岛素抵抗,有50％血糖升至8．3mmol/L以上;形成糖尿病的大鼠体重与对照组无明显区别;高脂饮食组瘦素与胰岛素水平与对照组比较有明显差异;所有大鼠瘦素水平与体重、胰岛素、血糖均呈正相关。结论：（1）高脂饮食是导致胰岛素抵抗形成糖尿病的诱因之一;（2）体脂含量与糖尿病正相关;（3）瘦素抵抗与胰岛素抵抗形成糖尿病的发病机制可能有关;（4）瘦素水平随着鼠龄的增加而增高,且参与体重的调节。     

Paraoxonase gene polymorphisms and coronary reactivity in young healthy men

This study examined the relationships between paraoxonase genotypes, coronary artery reactivity, and indices of low-density lipoprotein oxidation in healthy men. Impairment in coronary flow reserve, as assessed by positron emission tomography, is associated with lipoprotein oxidation, which is affected by high-density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme. Forty-nine healthy men (mean age 35 +/- 4 years) were divided by paraoxonase genotype into low (Q192/Q192, or M55/M55, M55/L55) and high-active (R192/Q192, R192/R192, or L55/L55) groups and related to the myocardial blood flow, to the susceptibility of low-density lipoprotein to oxidation, and the autoantibody titer against oxidized low-density lipoprotein. The blood flow was measured by positron emission tomography at rest and during adenosine infusion. The low-active Q192/Q192 genotype was associated with higher resting blood flow corrected for rate-pressure product compared to the high-active R192/R192 and R192/Q192 genotypes (P=0.011). The blood flow stimulated by adenosine was not significantly different in the low- and high-active genotype groups. Paraoxonase genotypes had no effect on low-density lipoprotein susceptibility to oxidation or autoantibody formation against oxidized low-density lipoprotein. Genotypes of paraoxonase may not clearly contribute to the early changes in coronary reactivity. Coronary vasomotor tone at rest appears to be modulated by paraoxonase R/Q192 polymorphism through mechanism(s) unrelated to low-density lipoprotein oxidation.     

短期高果糖喂养对小鼠肝脏脂质沉积和胰岛素敏感性的影响

目的: 探讨短期高果糖饮食对小鼠肝脏甘油三酯含量及胰岛素敏感性的影响。方法: 雄性C57BL/J6小鼠分为对照组及高果糖组,经喂养3 d后对小鼠行腹腔葡萄糖耐量试验,处死小鼠后测定各组肝脏甘油三酯含量,采用HE染色观察肝脏组织的病理改变;测定肝脏脂质合成酶类的蛋白表达,同时通过比较各组注射与未注射胰岛素的小鼠磷酸化Akt/总Akt (p-Akt/t- Akt)和磷酸化GSK-3α/β/总GSK-3α/β(p- GSK-3α/β/t- GSK-3α/β)表达变化评估肝脏胰岛素敏感性。结果: 喂养3 d后,与对照组相比,高果糖组葡萄糖耐量曲线下面积和肝腔甘油三酯均显著增加(均P<0.01),同时肝组织HE染色显示高果糖组小鼠肝细胞已有明显脂滴沉积;与对照组相比,高果糖组的乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(FAS)和硬脂酰辅酶A脱饱和酶-1(SCD-1)表达显著增加(均P<0.01);胰岛素注射后,与对照组相比,高果糖组的p-Akt/t-Akt及p-GSK-3α/β/t-GSK-3α/β均显著降低(均P<0.01)。结论: 3 d高果糖饮食即可引起肝脏脂质沉积,脂质沉积与果糖刺激FAS、ACC和SCD-1表达增加有关;肝脏脂质沉积的同时伴有肝脏胰岛素抵抗发生。     

Gonadal steroids and salivary IgA in healthy young women and men

Empirical evidence from clinical, nonhuman animal, and in vitro studies point to links between immune function and gonadal steroids, including potential androgenic immunosuppression and estrogenic immunoenhancement. This study was designed to test links between steroids and one marker of mucosal humoral immunity—immunoglobulin A (IgA) in healthy individuals, to facilitate comparisons with other species and clinical populations, as there are few existing studies with healthy humans that also allow gender/sex investigations. Participants (86 women, 91 men) provided a saliva sample for measurement of testosterone (T), estradiol (E₂), and IgA. Results showed that E₂ was significantly and positively correlated with IgA in women, and group analyses by E₂ quartile showed that this association was linear. No significant correlations or nonlinear associations were seen between T and IgA in men or women, or E₂ and IgA in men. Evidence from this study indicates that IgA and E₂ are significantly associated in healthy premenopausal women. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.     

Effects of short-term corticoid ingestion on food intake and adipokines in healthy recreationally trained men

In order to test the hypothesis that short-term corticoid intake alters food intake, body composition and adipokines secretion in healthy volunteers with regular sport practice, nutrient intake was assessed in eight male athletes with and without prednisolone (PRED, 60 mg/day for 1 week) ingestion in a random, double blind, crossover design. Body weight, body composition, adipokines (i.e., leptin, adiponectin and TNF-α), insulin and blood glucose were determined before and at the end of each treatment. PRED did not induce any significant change in body weight, body composition or food intake. Insulin and TNF-α were not significantly altered with PRED compared to placebo but blood glucose, leptin and adiponectin concentrations at rest appear significantly increased after PRED treatment (P < 0.05). Our data show that 1 week glucocorticoid treatment does not promote obesity in recreationally trained men but further studies are necessary to understand its effects on the metabolically active hormones, leptin and adiponectin.     

Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding

A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism. The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a "microbial organ" localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.     

Costamere remodeling with muscle loading and unloading in healthy young men

Costameres are mechano-sensory sites of focal adhesion in the sarcolemma that provide a structural anchor for myofibrils. Their turnover is regulated by integrin-associated focal adhesion kinase (FAK). We hypothesized that changes in content of costamere components (beta 1 integrin, FAK, meta-vinculin, gamma-vinculin) with increased and reduced loading of human anti-gravity muscle would: (i) relate to changes in muscle size and molecular parameters of muscle size regulation [p70S6K, myosin heavy chain (MHC)1 and MHCIIA]; (ii) correspond to adjustments in activity and expression of FAK, and its negative regulator, FRNK; and (iii) reflect the temporal response to reduced and increased loading. Unloading induced a progressive decline in thickness of human vastus lateralis muscle after 8 and 34 days of bedrest (−4% and −14%, respectively; n = 9), contrasting the increase in muscle thickness after 10 and 27 days of resistance training (+5% and +13%; n = 6). Changes in muscle thickness were correlated with changes in cross-sectional area of type I muscle fibers (r = 0.66) and beta 1 integrin content (r = 0.76) at the mid-point of altered loading. Changes in meta-vinculin and FAK-pY397 content were correlated (r = 0.85) and differed, together with the changes of beta 1 integrin, MHCI, MHCII and p70S6K, between the mid- and end-point of resistance training. By contrast, costamere protein level changes did not differ between time points of bedrest. The findings emphasize the role of FAK-regulated costamere turnover in the load-dependent addition and removal of myofibrils, and argue for two phases of muscle remodeling with resistance training, which do not manifest at the macroscopic level.     

Classical conditioning and conditionability of insulin and glucose effects in healthy humans

We examined whether the effects of intravenously injected insulin and glucose (the physiological endogenous insulin production stimulus) could be classically conditioned in healthy humans. We expected a conditioned blood glucose decrease to a conditioned stimulus (CS) previously paired with insulin and an, albeit lower, blood glucose decrease to a CS paired with glucose injection. In addition, we analyzed glucoregulatory hormone and symptom conditionability. Thirty healthy males were divided into three groups and were given the CS and an intravenous injection of either insulin (0.05 IU/kg) in Group 1, glucose (15%, 0.5 g/kg) in Group 2, or placebo [physiological saline (0.9%)] in Group 3 during the acquisition phase on 4 days. All participants were given the olfactory CS (rosewood-peppermint smell) and placebo injection on Day 5 (test). On Day 5, the total blood glucose decrease tended to be higher in Group 1 than in Group 3 (P<.10), especially at CS presentation (P<.10) and previous unconditioned hypoglycemia time-point (P<.05). The conditioned blood glucose decrease was statistically nonsignificant in Group 2, but shortly after CS presentation, insulin level and blood glucose changes were negatively correlated in Groups 1 and 2 in contrast to positive correlation in Group 3. Furthermore, Group 1 showed an increase in noradrenaline (P<.05), a temporarily delayed increase in growth hormone (GH; P<.05), and an increase of autonomic and neuroglycopenic symptoms, reaching a medium and small effect size, respectively. Group 2 responded with an increase in cortisol (P<.01) and neuroglycopenic symptoms (P<.05) at the time-point of the previous unconditioned blood glucose minimum. To conclude, the effects of exogenously applied insulin can be conditioned in a reliable way. In correspondence with the lower intensity of the unconditioned stimulus (US), conditioning effects with glucose-and, thus, endogenously produced insulin-are weaker but also reflect the actions of central insulin. Future studies will examine the diverse actions of insulin within the brain further.     

Effect of diet restriction on glucose metabolism and insulin responsiveness in aging rats

The effect of age and of prolonged caloric restriction on glucose tolerance and insulin responsiveness has been studied in male Fischer 344 rats. Beginning at 1 month of age dietary intake of an experimental group (R) was limited to 60% of that of the control group (AL) which was allowed to eat ad libitum. Studies were carried out at intervals up to 24 months of age. In AL rats the oral glucose tolerance curve showed progressively higher peak levels of plasma glucose with age, and a decrease in the plasma insulin concentration at the time of the glucose peak. The R group did not show the increase in peak value with age and the corresponding insulin concentration was lower than that of the AL group. These results are compatible with a delay in the first phase of insulin secretion in aging AL rats. Insulin-stimulated glucose disposal was assessed by the method of Reaven et al. [Diabetes, 32 (1983) 175], at ages 4, 12, 18 and 24 months; using infusions of 2 mU of insulin and 1 mg of glucose/min per kg, the steady-state plasma glucose level (SSPG) was slightly lower in R than in AL rats, while the steady-state plasma insulin level was reduced by 40-60%. In rats aged 18-24 months the hepatic glucose output, measured with [3-3H]glucose, was the same for AL and R rats in the basal state and was reduced to the same extent by insulin. In the presence of epinephrine and propranolol, infusion of glucose and insulin at various rates demonstrated that the plasma glucose clearance rate increased linearly with increasing SSPI, and at comparable SSPI levels was lower in R than in AL rats. The ability of insulin to stimulate glycogenesis from glucose was measured in primary hepatocyte cultures. Insulin increased glycogenesis 3-fold in cells from AL rats and 4-6-fold in cells from R rats. There was no effect of age. The increased insulin responsiveness of R rats was not due to an increase in insulin binding or to a decrease in insulin degradation (measured with intact cells or as cytosolic insulinase activity).(ABSTRACT TRUNCATED AT 400 WORDS)