Visceral-to-peripheral adiposity ratio: a critical determinant of sex and ethnic differences in cardiovascular risks among Asian Indians and African Creoles in Mauritius.

BACKGROUND/AIMS: Coronary heart disease morbidity and mortality are higher in people of South Asian origin than in those of African origin. We investigated whether as young adults without diabetes, people in Mauritius of South Asian descent (Indians) would show a more adverse cardiovascular risk profile that those of predominantly African descent (Creoles), and whether this could be explained by ethnic differences in visceral adiposity or other fat distribution patterns. METHODS: The study was conducted in 189 young non-physically active adults, with the following measurements conducted after an overnight fast: anthropometry (weight, height, waist circumference), whole-body and regional body composition by dual-energy x-ray absorptiometry, blood pressure, and blood assays for glycemic (glucose and HbA1c) and lipid profile (triglycerides and cholesterols). RESULTS: The results indicate higher serum triglycerides and lower HDL cholesterol in men than in women, and in Indians than in Creoles (p < 0.001). No significant differences due to sex or ethnicity are observed in body mass index and waist circumference, but indices of visceral adiposity (visceral/android, visceral/subcutaneous) and visceral-to-peripheral adiposity ratio (visceral/gynoid, visceral/limb) were significantly higher in men than in women, and in Indians than in Creoles. The significant effects of sex and ethnicity on blood lipid profile were either completely abolished or reduced to a greater extent after adjusting for the ratio of visceral-to-peripheral adiposity than for visceral adiposity per se. CONCLUSIONS: In young adults in Mauritius, Indians show a more adverse pattern of body fat distribution and blood lipid risk profile than Creoles. Differences in their fat distribution patterns, however, only partially explain their differential atherogenic lipid risk profile, amid a greater impact of visceral-to-peripheral adiposity ratio than that of visceral adiposity per se on sex and ethnic differences in cardiovascular risks; the former possibly reflecting the ratio of hazardous (visceral) adiposity and protective (peripheral) superficial subcutaneous adiposity.

Sucrose dampens caffeine-induced blood pressure elevations - A randomized crossover pilot study in healthy, non-obese men.

Purpose: Sales for sugar-sweetened and caffeinated beverages are still rising globally and their consumption has been linked to the development of cardiovascular diseases. However, direct evidence from human interventional studies in response to such beverages is still scarce. Methods: Seven young, non-obese men participated in a randomized crossover study where four test drinks [60 g sucrose + 50 mg caffeine, 60 g sucrose + caffeine-placebo, 50 mg caffeine, and caffeine-placebo] were investigated. Each drink was brought to a total volume of 500 mL with water. Continuous and beat-to-beat hemodynamic monitoring was conducted for 30 min baseline and continued for 90 min after the ingestion of each drink. Measurements included blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, index of contractility, and double product. Results: Two-factor ANOVA analysis revealed significant treatment-by-time effects for diastolic blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, index of contractility, and double product (all p < 0.01). Diastolic blood pressure and total peripheral resistance increased significantly to caffeine-only (all p < 0.05), while sucrose + caffeine-placebo and sucrose + caffeine both decreased resistance responses (all p < 0.05). Cardiac output increased significantly to sucrose + caffeine-placebo and sucrose + caffeine (all p < 0.05), and on trend for heart rate, stroke volume, and index of contractility (all p between 0.05 and 0.09). Conclusion: In young, non-obese men, a caffeinated and sucrose-sweetened beverage at concentrations similar to classical commercial Cola products exhibited distinct hemodynamic actions where the presence of sucrose dampened caffeine-induced blood pressure elevations, but at the expense of a tendency to increase cardiac work.

Dynamics of Fat Oxidation from Sitting at Rest to Light Exercise in Inactive Young Humans.

Societal erosion of daily life low-level physical activity has had a great influence on the obesity epidemic. Given that low fat oxidation is also a risk factor for obesity, we investigated, in a repeated measures design, the dynamics of fat oxidation from a resting state to a light-intensity leg cycling exercise (0-50 watts) in inactive, healthy young adults. Using indirect calorimetry, energy expenditure and the respiratory quotient (RQ) were assessed in a sitting posture at rest and during a cycling exercise in 35 subjects (20 women). The rate of perceived exhaustion (RPE) was assessed using the Borg Scale. During graded leg cycling, the mean RPE did not exceed values corresponding to the exercise being perceived as 'light'. However, analysis of individual data at 50 watts revealed two distinct subgroups among the subjects: those having RPE values corresponding to the exercise being perceived as 'very light to light' and showing no increase in RQ relative to resting levels, as opposed to an increase in RQ in those who perceived the exercise as being 'somewhat hard to hard' (p < 0.001). Our study in inactive individuals showing that high fat oxidation was maintained during 'light-perceived' physical activity reinforced the potential importance of light physical activity in the prevention of obesity.

Pathogenesis of obesity and cardiometabolic diseases: From the legacy of Ancel Keys to current concepts.

Several areas of research into the prevention and treatment of obesity today can be traced to one or more of the scientific works pioneered by Ancel Keys between the 1930s to 1970s in fields that cut across the physiology of extremes and public health nutrition. These range from his classical studies into how body and mind respond to chronic exposure to hypoxia in "The Physiology of Life at High Altitudes" or to simulated famine under controlled laboratory conditions in "The Biology of Human Starvation", the impact of diet and lifestyle on cardiovascular morbidity and mortality in "The Seven Countries Study," to the "Indices of Relative Weight and Obesity" in which he identified what has since been the most widely utilized diagnostic tool to monitor obesity across populations worldwide and which he coined as the body mass index. The contribution of Ancel Keys to medical sciences through his observations, analytical approaches, and research output of his classic studies, and how these have (and continue) to impact on a plethora of current concepts in obesity research today, are embodied in the eight review articles that constitute this supplement reporting the proceedings of the 10th Fribourg Obesity Research Conference. The aim of this introductory paper is to put into perspective the legacy of Ancel Keys to current concepts that are encapsulated in these review articles that cover research areas that include (i) the diagnosis of obesity for health risks; (ii) the role of dietary fat types in the pathogenesis of obesity and cardiometabolic diseases; (iii) the rationale, efficacy and safety of low carbohydrate ketogenic diets, or the therapeutic potential of hypoxic conditioning, in weight management programs; (iv) the psychological and physiological basis of the "famine reaction" that counters therapeutic dieting and facilitates weight regain; and (v) the potential impact of weight cycling and yoyo dieting on risks for later obesity and cardiometabolic diseases.

Ancel Keys: The legacy of a giant in physiology, nutrition, and public health.

Ancel Keys, whose life spanned over 100 years (1904-2004), made a wealth of seminal scientific and public health contributions. As a physiologist, nutritionist, and public health scientist, he has left his mark on the 20th century by exploring different areas of physiology and nutrition, as well as by contributing to the understanding of basic public health issues. Among his major achievements one can mention in chronological order: studying adaptation to very high altitude, developing the K ration to enable the US military to survive with light but dense food, dissecting the physiology of starvation and nutritional rehabilitation to optimize recovery of functions, uncovering the link between serum cholesterol and heart disease, coordinating the first multi-country epidemiological longitudinal study in nutrition and health, coining the word "body mass index" (BMI), which he showed to be the best body weight index to predict body fat, and promoting the Mediterranean diet for a healthy life style. This review examines the historical events and scientific intrigues that have surrounded Ancel Keys's major classical studies that have ensured him a central place in the history of medical science.

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets?

The most appropriate type of diets to maintain or lose body weight over the medium to long term has been a matter of controversy and debates for more than half a century. Both voluntarily and coercive food restriction, resulting in negative energy and macronutrient balance and hence weight loss, have not been designed to be maintained for the long term. By contrast, when a classical and traditional type of alimentation is consumed in ad lib conditions (e.g., the Mediterranean "diet"), it generally provides an appropriate nutritional density of essential macronutrients and micronutrients; it is hence appropriate for long-term use, and it provides several benefits for health if the compliance of the individuals is maintained over time. In this short review, we focus on four specific aspects: first, the need to agree on a clear definition of what is "low" versus "high" in terms of total carbohydrate intake and total fat intakes, both generally inversely related, in a representative individual with a certain lifestyle and a certain body morphology; second, the importance of discussing the duration over which it could be prescribed, that is, acute versus chronic conditions, focusing on the comparison between the fashion and often ephemeral low-carbohydrate diet (acute) with the well-recognized traditional Mediterranean type of alimentation (chronic), which includes lifestyle changes; third, the particular metabolic characteristics induced by the low-carbohydrate (high fat) diet, namely, the scramble up of ketone bodies production. The recent debate on ketogenic diets concern whether or not, in iso-energetic conditions, low-carbohydrate diets would significantly enhance energy expenditure. This is an issue that is more "academic" than practical, on the ground that the putative difference of 100-150 kcal/day or so (in the recent studies) is not negligible but within the inherent error of the methodology used to track total energy expenditure in free living conditions by the doubly labeled water technique. Fourth, the potential medical risks and shortcomings of ingesting (over the long term) low-carbohydrate ketogenic diets could exacerbate underlying renal dysfunction, consecutive to the joint combination of high-fat, high-protein diets, particularly in individuals with obesity. This particular diet promotes metabolic acidosis and renal hyperfiltration, which ultimately may contribute to a significant reduction in life expectancy in middle-age people.

How dieting might make some fatter: modeling weight cycling toward obesity from a perspective of body composition autoregulation.

The notion that dieting makes some people fatter has in the past decade gained considerable interest from both epidemiological predictions and biological plausibility. Several large-scale prospective studies have suggested that dieting to lose weight is associated with future weight gain and obesity, with such predictions being stronger and more consistent among dieters who are in the normal range of body weight rather than in those with obesity. Furthermore, the biological plausibility that dieting predisposes people who are lean (rather than those with overweight or obesity) to regain more body fat than what had been lost (referred to as fat overshooting) has recently gained support from a re-analysis of data on body composition during weight loss and subsequent weight recovery from the classic longitudinal Minnesota Starvation Experiment. These have revealed an inverse exponential relationship between the amount of fat overshot and initial adiposity, and have suggested that a temporal desynchronization in the recoveries of fat and lean tissues, in turn residing in differences in lean-fat partitioning during weight loss vs. during weight recovery (with fat recovery faster than lean tissue recovery) is a cardinal feature of fat overshooting. Within a conceptual framework that integrates the relationship between post-dieting fat overshooting with initial adiposity, the extent of weight loss and the differential lean-fat partitioning during weight loss vs. weight recovery, we describe here a mathematical model of weight cycling to predict the excess fat that could be gained through repeated dieting and multiple weight cycles from a standpoint of body composition autoregulation.

Body composition-derived BMI cut-offs for overweight and obesity in ethnic Indian and Creole urban children of Mauritius.

It is increasingly recognised that the use of BMI cut-off points for diagnosing obesity (OB) and proxy measures for body fatness in a given population needs to take into account the potential impact of ethnicity on the BMI-fat % relationship in order to avoid adiposity status misclassification. This relationship was studied here in 377 Mauritian schoolchildren (200 boys and 177 girls, aged 7-13 years) belonging to the two main ethnic groups: Indian (South Asian descent) and Creole (African/Malagasy descent), with body composition assessed using an isotopic 2H dilution technique as reference. The results indicate that for the same BMI, Indians have more body fat (and less lean mass) than Creoles among both boys and girls: linear regression analysis revealed significantly higher body fat % by 4-5 units (P < 0·001) in Indians than in Creoles across a wide range of BMI (11·6-34·2 kg/m2) and body fat % (5-52 %). By applying Deurenberg's Caucasian-based equation to predict body fat % from WHO-defined BMI thresholds for overweight (OW) and OB, and by recalculating the equivalent BMI values using a Mauritian-specific equation, it is shown that the WHO BMI cut-offs for OB and OW would need to be lowered by 4·6-5·9 units in Indian and 2·0-3·7 units in Creole children in the 7-13-year-old age group. These results have major implications for ethnic-based population research towards improving the early diagnosis of excess adiposity in this multi-ethnic population known to be at high risk for later development of type 2 diabetes and CVD.

Cardiovascular and Orthostatic Responses to a Festive Meal Associated With Alcohol in Young Men.

Aim: Sharing a festive meal associated with alcohol is quite common. While the cardiovascular changes occurring after meal ingestion of different nutrient composition has been well-established, the effects of ingesting a festive versus a standard meal accompanied with alcohol are less clear. Here, we compared the postprandial hemodynamics, cutaneous and psychomotor performance responses after ingestion of a classical Swiss festive meal [cheese fondue (CF)] versus a light ready-meal [Nasi Goreng (NG)], both accompanied with white wine. Methods: In a randomized cross over design, we examined in 12 healthy young men, the continuous cardiovascular, cutaneous, and reaction time responses to ingestion of cheese fondue versus a standard meal at rest (sitting position) and hemodynamic changes in response to orthostatic challenge (active standing) in pre- and postprandial phases. Results: Breath alcohol concentration after wine ingestion was similar after both meal types. Compared to the standard meal, consumption of CF induced higher increases in heart rate (HR), cardiac output (CO), double product (DP) and cardiac power output (CPO), greater vasodilation, and rises in skin blood flow and skin temperature. Greater increases in HR, DP, and mean blood pressure (MBP) were observed during orthostatic challenges with CF compared to NG. A two-choice reaction time task revealed similar reaction times with both meals, suggesting no influence of meal composition on psychomotor performance. Conclusion: In sitting position, CF ingestion induced a more important cardiovascular load compared to NG. Although the dose of alcohol and the festive meal used here did not lead to orthostatic hypotension, eating CF induced a greater cardiometabolic load suggesting that hemodynamic reserves have been encroached during active standing. This may impede the cardiovascular capacity during physical exercise or stress situations, particularly in elderly subjects who are at greater risk for postprandial hypotension and cardiovascular diseases.

Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction.

The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs. lean mass recovery, with this phenomenon of "preferential catch-up fat" being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill system, with telemetry capsules implanted in the peritoneal cavity, was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24-h Tc was reduced in response to semistarvation (-0.77°C, P < 0.001) and remained significantly lower than in control animals during the catch-up fat phase of refeeding (-0.27°C on average, P < 0.001), the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24-h cycle (-0.30°C vs. -0.23°C, P < 0.01) and with no between-group differences in locomotor activity. A lower 24-h Tc in animals showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e., at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth.

Assessment of the Dose-Response Relationship between Meal Protein Content and Postprandial Thermogenesis: Effect of Sex and the Oral Contraceptive Pill.

Implementation of efficacious dietary interventions to regulate energy balance requires understanding of the determinants of individual response. To date, information regarding individual variability in response to elevated meal protein content is lacking. This study investigates whether sex and/or oral contraceptive pill (OCP) use play a role in the response to elevated meal protein in 21 healthy young adults (seven men, seven women not taking OCP, and seven women who were OCP users). Participants consumed each of three standardized isocaloric (590 kcal) meals of differing protein content (11, 23, 31% kcal protein). Resting energy expenditure (EE), respiratory quotient (RQ), hunger and satiety were measured at baseline (fasting) and during 180 min postprandial. Whilst significant dose-response increases in EE were observed in men, meal protein-induced EE in women without OCP reached a maximum at <23% protein. Women taking OCP reported lower postprandial fullness than women without OCP, despite similar body size, but also, most notably, no significant difference in EE response between any of the meals. Whilst the mechanisms underpinning this thermogenic inflexibility in response across a wide-range (three-fold) of protein meal content require further investigation, this highlights the need for careful consideration of factors that may influence an individual's metabolic response to dietary interventions aimed at optimising postprandial thermogenesis for body weight regulation.

Reduced Skeletal Muscle Protein Turnover and Thyroid Hormone Metabolism in Adaptive Thermogenesis That Facilitates Body Fat Recovery During Weight Regain.

Objective: The recovery of body composition after weight loss is characterized by an accelerated rate of fat recovery (preferential catch-up fat) resulting partly from an adaptive suppression of thermogenesis. Although the skeletal muscle has been implicated as an effector site for such thrifty (energy conservation) metabolism driving catch-up fat, the underlying mechanisms remain to be elucidated. We test here the hypothesis that this thrifty metabolism driving catch-up fat could reside in a reduced rate of protein turnover (an energetically costly "futile" cycle) and in altered local thyroid hormone metabolism in skeletal muscle. Methods: Using a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis, we measured after 1 week of refeeding in refed and control animals the following: (i) in-vivo rates of protein synthesis in hindlimb skeletal muscles using the flooding dose technique of 13C-labeled valine incorporation in muscle protein, (ii) ex-vivo muscle assay of net formation of thyroid hormone tri-iodothyronine (T3) from precursor hormone thyroxine (T4), and (iii) protein expression of skeletal muscle deiodinases (type 1, 2, and 3). Results: We show that after 1 week of calorie-controlled refeeding, the fractional protein synthesis rate was lower in skeletal muscles of refed animals than in controls (by 30-35%, p < 0.01) despite no between-group differences in the rate of skeletal muscle growth or whole-body protein deposition-thereby underscoring concomitant reductions in both protein synthesis and protein degradation rates in skeletal muscles of refed animals compared to controls. These differences in skeletal muscle protein turnover during catch-up fat were found to be independent of muscle type and fiber composition, and were associated with a slower net formation of muscle T3 from precursor hormone T4, together with increases in muscle protein expression of deiodinases which convert T4 and T3 to inactive forms. Conclusions: These results suggest that diminished skeletal muscle protein turnover, together with altered local muscle metabolism of thyroid hormones leading to diminished intracellular T3 availability, are features of the thrifty metabolism that drives the rapid restoration of the fat reserves during weight regain after caloric restriction.

Early and Late Cardiovascular and Metabolic Responses to Mixed Wine: Effect of Drink Temperature.

Aim: Red wine is usually ingested as an unmixed drink. However, mixtures of wine with juices and/or sucrose (mixed wine) are becoming more and more popular and could be ingested at either cold or hot temperature. Although the temperature effects on the cardiovascular system have been described for water and tea, with greater energy expenditure (EE) and lower cardiac workload with a colder drink, little information is available on the impact of temperature of alcoholic beverages on alcoholemia and cardiometabolic parameters. The purpose of the present study was to compare the acute cardiovascular and metabolic changes in response to mixed wine ingested at a cold or at a hot temperature. Methods: In a randomized crossover design, 14 healthy young adults (seven men and seven women) were assigned to cold or hot mixed wine ingestion. Continuous cardiovascular, metabolic, and cutaneous monitoring was performed in a comfortable sitting position during a 30-min baseline and for 120 min after ingesting 400 ml of mixed wine, with the alcohol content adjusted to provide 0.4 g ethanol/kg of body weight and drunk at either cold (3°C) or hot (55°C) temperature. Breath alcohol concentration was measured intermittently throughout the study. Results: Overall, alcoholemia was not altered by drink temperature, with a tendency toward greater values in women compared to men. Early responses to mixed wine ingestion (0-20 min) indicated that cold drink transiently increased mean blood pressure (BP), cardiac vagal tone, and decreased skin blood flow (SkBf) whereas hot drink did not change BP, decreased vagal tone, and increased SkBf. Both cold and hot mixed wine led to increases in EE and reductions in respiratory quotient. Late responses (60-120 min) led to similar cardiovascular and metabolic changes at both drink temperatures. Conclusion: The magnitude and/or the directional change of most of the study variables differed during the first 20 min following ingestion and may be related to drink temperature. By contrast, late changes in cardiometabolic outcomes were similar between cold and hot wine ingestion, underlying the typical effect of alcohol and sugar intake on the cardiovascular system.

Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.

Type-II l-arginine:ureahydrolase, arginase-II (Arg-II), is abundantly expressed in the kidney. The physiologic role played by Arg-II in the kidney remains unknown. Herein, we report that in mice that are deficient in Arg-II (Arg-II-/-), total and membrane-associated aquaporin-2 (AQP2) protein levels were significantly higher compared with wild-type (WT) controls. Water deprivation enhanced Arg-II expression, AQP2 levels, and membrane association in collecting ducts. Effects of water deprivation on AQP2 were stronger in Arg-II-/- mice than in WT mice. Accordingly, a decrease in urine volume and an increase in urine osmolality under water deprivation were more pronounced in Arg-II-/- mice than in WT mice, which correlated with a weaker increase in plasma osmolality in Arg-II-/- mice. There was no difference in vasopressin release under water deprivation conditions between either genotype of mice. Although total AQP2 and phosphorylated AQP2-S256 levels (mediated by PKA) in kidneys under water deprivation conditions were significantly higher in Arg-II-/- mice compared with WT animals, there is no difference in the ratio of AQP2-S256:AQP2. In cultured mouse collecting duct principal mCCDcl1 cells, expression of both Arg-II and AQP2 were enhanced by the vasopressin type 2 receptor agonist, desamino- d-arginine vasopressin (dDAVP). Silencing Arg-II enhanced the expression and membrane association of AQP2 by dDAVP without influencing cAMP levels. In conclusion, in vivo and in vitro experiments demonstrate that Arg-II negatively regulates AQP2 and the urine-concentrating capability in kidneys via a mechanism that is not associated with the modulation of the cAMP pathway.-Huang, J., Montani, J.-P., Verrey, F., Feraille, E., Ming, X.-F., Yang, Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.

The contribution of Swiss scientists to the assessment of energy metabolism.

Although Switzerland is considered a small country, it has its share in discoveries, inventions and developments for the assessment of energy metabolism. This includes seminal contributions to respiratory and metabolic physiology and to devices for measuring energy expenditure by direct and indirect calorimetry in vivo in humans and small animals (as well as in vitro in organs/tissues), for the purpose of evaluating the basic nutritional requirements. A strong momentum came during World War II when it was necessary to evaluate the energy requirements of soldiers protecting the country by assessing their energy expenditure, as well as to determine the nutritional needs of the Swiss civil population in time of war when food rationing was necessary to ensure national neutrality and independence. A further impetus came in the 1970s at the start of the obesity epidemics, toward a better understanding of the metabolic basis of obesity, ranging from the development of whole-body concepts to molecular mechanisms. In a trip down memory lane, this review focuses on some of the earlier leading Swiss scientists who have contributed to a better understanding of the field.

Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min-1; hot tea: -1 ± 1 beats.min-1, p < 0.05), double product, skin blood flow and hand temperature and (2) an increase in baroreflex sensitivity, fat oxidation and energy expenditure (cold tea: +8.3%; hot tea: +3.7%, p < 0.05). Averaged over the 90 min post-drink ingestion, we observed no differences of tea temperature on cardiac output work and mean blood pressure responses. Conclusion: Ingestion of an unsweetened caffeinated herbal tea at cold temperature induced a greater stimulation of thermogenesis and fat oxidation than hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis.

Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway. Silencing Myo1b prevents all these alterations induced by Arg-II. By overexpressing Myo1b or its mutant with point mutation in its pleckstrin homology (PH) domain we further demonstrate that this effect of Myo1b is dependent on its PH domain that is required for Myo1b-lysosome association. Notably, Arg-II promotes association of Myo1b with lysosomes. In addition, we show that in senescent vascular smooth muscle cells with elevated endogenous Arg-II, silencing Myo1b prevents Arg-II-mediated lysosomal positioning, dissociation of TSC from lysosome, mTORC1 activation and cell apoptosis. Taken together, our study demonstrates that Myo1b mediates the effect of Arg-II in activating mTORC1-S6K1 through promoting peripheral lysosomal positioning, that results in spatial separation and thus dissociation of TSC from lysosome, leading to hyperactive mTORC1-S6K1 signaling linking to cellular senescence/apoptosis.

Cardiovascular and Cutaneous Responses to the Combination of Alcohol and Soft Drinks: The Way to Orthostatic Intolerance?

Aim: Acute ingestion of alcohol is often accompanied by cardiovascular dysregulation, malaise and even syncope. The full hemodynamic and cutaneous responses to the combination of alcohol and sugar (i.e., alcopops), a common combination in young people, and the mechanisms for the propensity to orthostatic intolerance are not well established. Thus, the purpose of this study was to evaluate the cardiovascular and cutaneous responses to alcopops in young subjects. Methods: Cardiovascular and cutaneous responses were assessed in 24 healthy young subjects (12 men, 12 women) sitting comfortably and during prolonged active standing with a 30-min baseline and 130 min following ingestion of 400 mL of either: water, water + 48 g sugar, water + vodka (1.28 mL.kg-1 of body weight, providing 0.4 g alcohol.kg-1), water + sugar + vodka, according to a randomized cross-over design. Results: Compared to alcohol alone, vodka + sugar induced a lower breath alcohol concentration (BrAC), blood pressure and total peripheral resistance (p < 0.05), a higher cardiac output and heart rate (p < 0.05) both in sitting position and during active standing. In sitting position vodka + sugar consumption also led to a greater increase in skin blood flow and hand temperature (p < 0.05) and a decrease in baroreflex sensitivity (p < 0.05). We observed similar results between men and women both in sitting position and during active standing. Conclusion: Despite lower BrAC, ingestion of alcopops induced acute vasodilation and hypotension in sitting position and an encroach of the hemodynamic reserve during active standing. Even if subjects did not feel any signs of syncope these results could be of clinical importance with higher doses of alcohol or if combined to other hypotensive challenges.