Changes In Substrate Metabolism Research Articles

Effects of long-term periodized carbohydrate intake on body composition, substrate metabolism and running performance in recreational active men: A pilot trial

Introduction & Purpose It is important to consider the impact of nutrition on training adaptations and performance outcomes (Jeukendrup, 2017). The present study was therefore conducted with the objective of determining whether long-term periodizing carbohydrate (CHO) intake during an eight-week endurance training plan has any benefit in comparison to a traditional high-CHO or low-CHO diet in terms of running performance, substrate metabolism and body composition in recreational active males. Methods In a controlled, randomised, parallel-group and free-living design, recreationally active runners (n = 24, VO2 peak: 51 ± 8 mL·min-1·kg-1) completed 8 weeks of an ad-libitum dietary intervention (LCHF[low CHO, high fat]/CHO: 4-week regimen with ≤ 50 g CHO per day directly followed by a 4-week regimen comprising 50-60% of daily energy intake from CHO, n = 8; CHO/CHO: 8-week regimen comprising 50-60% of daily energy intake from CHO, n = 9; LCHF/LCHF: 8-week regimen with ≤ 50 g CHO per day, n = 7) together with 5 prescribed sessions of an endurance training program. Dietary recalls were conducted 3 times a week. Body composition, performance and substrate metabolism were assessed 3 times during the study (T -0, T -1 and T -2) using bioelectric impedance and a graded exercise test on a treadmill starting at 6 km·h−1 with increasing speed by 1.5 km·h−1 every 3 minutes until exhaustion. Data were analysed using a 2-way mixed ANOVA and are presented as mean ± STD. Significance was set at p < 0.05. Results Peak running speed (PRS) and time to exhaustion (TTE) demonstrated an increase over time, with no additional benefit observed in relation to any group. Total fat oxidation and maximum fat oxidation (MFO) increased in the first half of the LCHF/CHO diet and decreased during the CHO rich diet (p < 0.001). In LCHF/LCHF fat oxidation and MFO increased from T -0 to T -1 (p < 0.001) and remained unchanged at T -2. In CHO/CHO no changes in fat oxidation or MFO were observed (p > 0.05). Total fat oxidation and MFO were significantly higher at T -1 in LCHF/CHO and LCHF/LCHF compared to CHO/CHO (p < 0.05). However, at T -2 fat oxidation and MFO were significantly higher in LCHF/LCHF compared to LCHF/CHO and CHO/CHO (p < 0.05). Significant reductions in weight, BMI, and absolute fat mass were observed in LCHF/CHO from T -0 to T -1 (p < 0.05) without any further changes until T -2. For LCHF/LCHF weight and BMI were significantly reduced in the first four weeks (p < 0.001) and even further reduced in the second half (p < 0.05). For CHO/CHO no significant changes in body composition were observed (p > 0.05). Discussion & Conclusion As previously noted, a high-fat diet resulted in a greater reliance on fat oxidation during exercise (Cao et al., 2021). Here, long-term periodisation of CHO according to the preferred training adaptation leads to changes in substrate metabolism during exercise in terms of improved fat oxidation during a LCHF diet and restoration of CHO oxidation during a CHO-rich diet. Despite the observed improvements in PRS and TTE over the course of the study, no significant advantage was demonstrated by any of the groups in comparison to the other trial groups. References Cao, J., Lei, S., Wang, X., & Cheng, S. (2021). The effect of a ketogenic low-carbohydrate, high-fat diet on aerobic capacity and exercise performance in endurance athletes: A systematic review and meta-analysis. Nutrients, 13(8), Article 2896. https://doi.org/10.3390/nu13082896 Jeukendrup, A. E. (2017). Periodized nutrition for athletes. Sports Medicine, 47(S1), 51-63. https://doi.org/10.1007/s40279-017-0694-2

Ferroptosis and aerobic training in ageing.

Ferroptosis is a form of programmed cell death that plays a significant role in causing several diseases such as heart attack and heart failure, through alterations in fat, amino acid, and iron metabolism. Comprehending the regulatory mechanisms of ferroptosis signaling is critical because it has a considerable effect on the elderly's mortality. Conversely, age-related changes in substrate metabolism and metabolite levels are recognized to give rise to obesity. Furthermore, research has proposed that aging and obesity-related changes in substrate metabolism may aggravate ferroptosis. The suppression of ferroptosis holds potential as a successful therapeutic approach for managing different diseases, including sarcopenia, cardiovascular diseases, and central nervous system diseases. However, the pathologic and biological mechanisms behind the function of ferroptosis are not fully comprehended yet. Physical activity could affect lipid, amino acid, and iron metabolism to modulate ferroptosis. The aim of this study is to showcase the current understanding of the molecular mechanisms leading to ferroptosis and discuss the role of aging and physical activity in this phenomenon.

High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic exercise.

Chronically adhering to high-fat ketogenic diets or consuming ketone monoester supplements elicits ketosis. Resulting changes in substrate metabolism appear to be drastically different between ketogenic diets and ketone supplements. Consuming a ketogenic diet increases fatty acid oxidation with concomitant decreases in endogenous carbohydrate oxidation. Increased fat oxidation eventually results in an accumulation of circulating ketone bodies, which are metabolites of fatty acids that serve as an alternative source of fuel. Conversely, consuming ketone monoester supplements rapidly increases circulating ketone body concentrations that typically exceed those achieved by adhering to ketogenic diets. Rapid increases in ketone body concentrations with ketone monoester supplementation elicit a negative feedback inhibition that reduces fatty acid mobilization during aerobic exercise. Supplement-derived ketosis appears to have minimal impact on sparing of muscle glycogen or minimizing of carbohydrate oxidation during aerobic exercise. This review will discuss the substrate metabolic and associated aerobic performance responses to ketogenic diets and ketone supplements.

Mistakes in assessing the nutrition of patients with chronic liver disease and practical recommendations on how to avoid them: essentials of the United European Gastroenterological Week (2021)

Malnutrition is common for patients with chronic liver disease (CLD), it significantly aggravates prognosis for their quality of life and overall survival. Liver cirrhosis (LC) is one of the most severe CLD manifestations. The main causes of malnutrition at CL include insufficient food intake (deficiency of nutrients, especially proteins), malabsorption, metabolic disorders (predominance of gluconeogenesis rather than glycogenolysis) and changes in substrate metabolism (hypermetabolism). Sarcopenia, which is defined by loss of muscle mass and function, is a major component of malnutrition in patients with cirrhosis. It is important to note that sarcopenia adversely affects the number and severity of complications, quality of life, the outcome of liver transplantation and the overall survival rate of patients with advanced liver disease.Physicians of different specialties should be aware of the clinical and prognostic relevance of nutritional status, how to promptly recognize malnutrition and sarcopenia in patients with liver cirrhosis and how to appropriately manage these conditions.This paper elucidates methods of assessment of the nutritional status of patients and screening for sarcopenia, the main pathogenetic links in sarcopenia development, dietary recommendations (including diet in case of hepatic encephalopathy development), tactics of curation of patients with eating disorders. Particular attention is paid to assessing the presence of eating disorders in the process of selection of patients for transplantation and for TIPS. Recommendations are given for educating the caregivers for patients with chronic liver disease and informing patients about the risks of developing sarcopenia/sarcopenic obesity.This article discusses some of the most common errors in assessing the diet of patients with chronic liver disease, as well as current practical recommendations based on evidence that will allow physicians to avoid possible future errors in the care of such patients.

Effect of Ethnicity on Changes in Fat and Carbohydrate Oxidation in Response to Short-Term High Intensity Interval Training (HIIT): A Pilot Study.

This study compared changes in substrate metabolism with high intensity interval training (HIIT) in women of different ethnicities. Twelve Caucasian (C) and ten Hispanic women (H) (age = 24 ± 5 yr) who were inactive completed nine sessions of HIIT at 85 percent peak power output (%PPO). Pre-training, changes in fat oxidation (FOx) and carbohydrate oxidation (CHOOx) during progressive cycling were measured on two days to compute the minimum difference (MD). This test was repeated after the last training session. Between baseline tests, estimates of FOx and CHOOx were not different (p > 0.05) and were highly related (intraclass correlation coefficient equal to 0.72 to 0.88), although the coefficient of variation of maximal fat oxidation (MFO) was equal to 30%. Training significantly increased MFO (p = 0.03) in C (0.19 ± 0.06 g/min to 0.21 ± 0.06 g/min, d = 0.66) and H (0.16 ± 0.03 g/min to 0.19 ± 0.03 g/min, d = 1.3) that was similar (p = 0.92) between groups. There was a significant interaction for FOx (p = 0.003) as it was only increased in H versus C, although both groups exhibited reduced CHO oxidation (p = 0.002) with training. Use of MD revealed that only 3 of 22 women show meaningful increases in MFO (>0.08 g/min). The preliminary data reveals that a small dose of low-volume HIIT does not alter fat and CHO oxidation and there is little effect of ethnicity on the response to training.

Endogenous versus exogenous carbohydrate oxidation measured by stable isotopes in pre-pubescent children plus 13C abundances in foods consumed three days prior

PurposeThe purposes of the present study were to (a) examine resting metabolism, substrate utilization, and endogenous versus exogenous carbohydrate (CHO) oxidation before and after 30-g rapidly-digesting carbohydrate (RDC) ingestion using indirect calorimetry and breath test analysis of stable isotope concentrations in pre-pubescent children and (b) report the 13C abundances in foods consumed for three days prior. MethodsNineteen children (n = 10 boys, n = 9 girls) at Tanner stage I or II participated (mean age ± 95% CI = 9.84 ± 0.77 y) in this study. Food was administered to the children for three days preceding their scheduled breath tests. Breath tests and indirect calorimetry were performed after an 8-h fast before and 60 min following consumption of a 30-g simple RDC drink consisting of maltodextrin and sucrose. Open circuit spirometry and indirect calorimetry monitored resting metabolism and CHO oxidation. Separate breath samples were taken every 15 min. Samples of all foods and breath samples were analyzed for 13C and 12C abundances with a stable-isotope mass spectrometer. Results13C in expired breath samples were −23.81 ± 1.64‰ at baseline and increased every 15 min after consumption of the CHO drink (p < 0.001–0.009). Cumulative total, endogenous, and exogenous CHO utilization increased during the post-prandial period (p < 0.001). Endogenous CHO oxidation was consistently greater than exogenous CHO oxidation (p < 0.001–0.002).Blood glucose was elevated from baseline at 30- and 60-min post-prandial (p < 0.001). Insulin did not change over time (p = 0.184). ConclusionsThe foods provided during the 3-day controlled diet effectively minimized 13C variation prior to metabolic testing. The 13C abundances of foods reported herein should serve as practical recommendations to reduce 13C intake before breath tests. While endogenous CHO oxidation remained greater in proportion to exogenous CHO oxidation, these findings suggest that even a relatively small amount of RDC can increase exogenous CHO oxidation and blood glucose in normal-weight children. To further examine shifts in endogenous versus exogenous CHO utilization, we recommend that future studies take steps to minimize 13C variation before breath tests and examine changes in substrate metabolism at rest and during exercise in normal weight and overweight pre-pubescent children. Clinical trial registration numberNCT03185884.

Lysosomal Biology and Function: Modern View of Cellular Debris Bin.

Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking. Recent studies have demonstrated lysosomes as a signaling node which sense, adapt and respond to changes in substrate metabolism to maintain cellular function. Lysosomal dysfunction not only influence pathways mediating membrane trafficking that culminate in the lysosome but also govern metabolic and signaling processes regulating protein sorting and targeting. In this review, we describe the current knowledge of lysosome in influencing sorting and nutrient signaling. We further present a mechanistic overview of intra-lysosomal processes, along with extra-lysosomal processes, governing lysosomal fusion and fission, exocytosis, positioning and membrane contact site formation. This review compiles existing knowledge in the field of lysosomal biology by describing various lysosomal events necessary to maintain cellular homeostasis facilitating development of therapies maintaining lysosomal function.

Abstract 183: Phosphodiesterase 9 Inhibition Improves Cardiometabolic Profile in Female Mice Independent of Estrogen Status

Approximately 6.5 million Americans are living with heart failure (HF) currently and the number of persons is projected to increase 46% by 2030. One particularly notable syndrome associated with increasingly severe obesity is called - Heart failure with a preserved ejection fraction (HFpEF); which represents half of all HF patients world-wide. Epidemiologic insights have provided incremental evidence that female sex is a stronger risk factor for HFpEF, particularly post-menopausal women. Loss of estrogen after menopause reduces estrogen receptor induced-NO-cGMP-PKG activation and consequently less benefit from Phosphodiesterase 5(PDE5) inhibition which principally hydrolyze NO-derived cGMP that appears compromised in HFpEF patients. PDE9 targets cGMP generated by Natriuretic peptide (NP) signaling and is significantly increased in hearts from HFpEF patients. This supports a role of PDE9 in the heart and its value as a therapeutic target for abnormalities relevant to HFpEF. We created a murine model of postmenopausal obesity and mild cardiac stress induced HFpEF. Genetic ablation or pharmacological inhibition of PDE9 conferred higher contractile performance with increased %EF, %FS and improved diastolic relaxation and filling. Echo-MRI analysis showed an improvement in whole body metabolism with significant decrease in percent body fat associated with enhanced O 2 consumption and increased energy expenditure. The mechanisms underlying the protective effects are increased mitochondrial function and enhanced expression of transcriptional regulators pgc1α and pparα, driving mitochondrial fatty acid oxidation and increased energy dissipation. Our work identifies for the first-time reversal of changes in substrate metabolism, and mitochondrial dynamics as a direct consequence of PDE9 inhibition in heart and fat. Proteomic analysis also revealed a dynamic cross-talk of PDE9 protein with biological networks of mitochondrial membrane proteins and proteins regulating cellular metabolism. This study greatly enhances our understanding of how the cGMP/PKG activation system can be modulated in females with reduced sex hormone- paving the way for gender-selective targeting in patients with obesity and HFpEF.

Effect Of Ethnicity On Change In Vo2max And Substrate Oxidation In Response To HIIT

INTRODUCTION: About 20% of adults meet the 2008 Physical Activity Guidelines and this lack of physical activity increases individuals' risk of heart disease, stroke, type-2 diabetes, and certain cancers which increases morbidity and all-cause mortality. Typically, moderate intensity continuous training (MICT) is prescribed to clients to improve overall fitness and health status, although a primary barrier to regular physical activity among sedentary individuals is lack of time. An alternative to MICT is high intensity interval training (HIIT) which significantly increases VO2max and fat oxidation, in turn improving exercise capacity and reducing health risks. One widely ignored aspect of individual response to exercise training is ethnicity, as there are minimal data examining the effect of ethnicity on responses to exercise training. PURPOSE: To determine if ethnicity alters adaptation to low volume HIIT in sedentary women. METHODS: Inactive, non-obese women (age and VO2max = 24.3 ± 4.1 yr and 29.1 ± 2.1 mL/kg/min) participated in 9 sessions over a 3-week period of cycling-based HIIT (8-10 1-minute bouts at 85% PPO interspersed with 75-sec recovery at 10% PPO). Participants were Caucasian (C) (n=6) or Hispanic (H) (n=4). To assess VO2max, the initial work rate began at 30 or 40 W for 2-min followed by a 15 or 20 W/min increase in power output until volitional exhaustion. To assess substrate oxidation, a 6-min warm up began at 10% PPO and subsequently work rate increased by 10% PPO every 5-min during 4 remaining stages. These variables were measured pre- and post-training. RESULTS: Training elicited a HR equal to 88-94% HRmax. Data showed an increase (p=0.016) in VO2max in C (30.5 ± 1.3 vs 32.6 ± 3.9 mL/kg/min, +7%) and H (27.7 ± 2.8 vs 31.7 ± 2.6 mL/kg/min, +14%) with no significant groupXtime interaction (p=0.35). There was a significant trainingXboutXgroup interaction for fat oxidation (p=0.005), carbohydrate oxidation (p=0.009), and RER (p=0.000). Data showed an increase in the rate of fat oxidation and a reduction in carbohydrate oxidation in response to training which differed based on ethnicity. CONCLUSION: These data show HIIT induces significant increases in VO2max which are slightly higher in H vs C. In addition, ethnicity seems to mediate changes in substrate metabolism after interval-based exercise.

Low-intensity exercise induces acute shifts in liver and skeletal muscle substrate metabolism but not chronic adaptations in tissue oxidative capacity.

Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 wk; 5 days/wk; 1 h/day) low-intensity treadmill exercise were tested in healthy male C57BL/6J mice. Low-intensity exercise maximizes lipid utilization; therefore, we hypothesized pathways involved in lipid metabolism would be most robustly affected. Acute exercise nearly depleted liver glycogen immediately postexercise (0 h), whereas hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3 h). Also, hepatic peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and fat oxidation (mitochondrial and peroxisomal) increased immediately postexercise (0 h), whereas carbohydrate and amino acid oxidation in liver peaked 24-48 h later. Alternatively, skeletal muscle exhibited a less robust response to acute exercise as stored substrates (glycogen and TAG) remained unchanged, induction of PGC-1α gene expression was delayed (up at 3 h), and mitochondrial substrate oxidation pathways (carbohydrate, amino acid, and lipid) were largely unaltered. Peroxisomal lipid oxidation exhibited the most dynamic changes in skeletal muscle substrate metabolism after acute exercise; however, this response was also delayed (peaked 3-24 h postexercise), and expression of peroxisomal genes remained unaffected. Interestingly, 6 wk of training at a similar intensity limited weight gain, increased muscle glycogen, and reduced TAG accrual in liver and muscle; however, substrate oxidation pathways remained unaltered in both tissues. Collectively, these results suggest changes in substrate metabolism induced by an acute low-intensity exercise bout in healthy mice are more rapid and robust in liver than in skeletal muscle; however, training at a similar intensity for 6 wk is insufficient to induce remodeling of substrate metabolism pathways in either tissue. NEW & NOTEWORTHY Effects of low-intensity exercise on substrate metabolism pathways were tested in liver and skeletal muscle of healthy mice. This is the first study to describe exercise-induced adaptations in peroxisomal lipid metabolism and also reports comprehensive adaptations in mitochondrial substrate metabolism pathways (carbohydrate, lipid, and amino acid). Acute low-intensity exercise induced shifts in mitochondrial and peroxisomal metabolism in both tissues, but training at this intensity did not induce adaptive remodeling of metabolic pathways in healthy mice.

Liver mitochondrial respiratory plasticity and oxygen uptake evoked by cobalt chloride in rats with low and high resistance to extreme hypobaric hypoxia

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (CoCl2) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. CoCl2 promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. CoCl2 diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by CoCl2. Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia.

Diabetic Cardiomyopathy: An Immunometabolic Perspective.

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) in cardiomyocytes, which is followed by apoptosis, changes in immune responses with a consequent increase in fibrosis, remodeling of cardiomyocytes, and the resultant decrease in cardiac function. The heart is an omnivore, metabolically flexible, and consumes the highest amount of ATP in the body. Altered myocardial substrate and energy metabolism initiate the development of DCM. Diabetic hearts shift away from the utilization of glucose, rely almost completely on fatty acids (FAs) as the energy source, and become metabolically inflexible. Oxidation of FAs is metabolically inefficient as it consumes more energy. In addition to metabolic inflexibility and energy inefficiency, the diabetic heart suffers from impaired calcium handling with consequent alteration of relaxation–contraction dynamics leading to diastolic and systolic dysfunction. Sarcoplasmic reticulum (SR) plays a key role in excitation–contraction coupling as Ca2+ is transported into the SR by the SERCA2a (sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a) during cardiac relaxation. Diabetic cardiomyocytes display decreased SERCA2a activity and leaky Ca2+ release channel resulting in reduced SR calcium load. The diabetic heart also suffers from marked downregulation of novel cardioprotective microRNAs (miRNAs) discovered recently. Since immune responses and substrate energy metabolism are critically altered in diabetes, the present review will focus on immunometabolism and miRNAs.

Substrate Utilization Effects on Shortening Properties in Aging Cardiac Myocytes

Aging is associated with declining cardiac contractile function as well as changes in substrate metabolism and mitochondrial function. The relationship between age‐related changes in cardiac metabolism and declining cardiac contractile function has not been determined. We explored the role of alterations in substrate metabolism on age‐related changes in contractile function of isolated left ventricular myocytes from Young (Y) and Old (O) FBN rats. Single, intact myocytes were stimulated for ten minutes of continuous contraction at either2Hz or 4Hz while being perfused with Ringers solution containing either Glucose (11mM) or Oleate (0.4mM) as the fuel substrate. Properties of shortening (% and rate of shortening) were measured at the onset (T0) and after 10 minutes (T10) of continuous contraction, and the decline in shortening over time (T10/T0) was determined at each workload. Myocytes from Y hearts generally had better contractile function when glucose was the substrate, with a smaller workload‐dependent decline in function, compared to when oleate was the substrate. In aged myocytes, the opposite was true, with O myocytes showing less workload‐dependent decline in percent shortening and rate of shortening when oleate was the substrate. This data suggests that when forced to use only one substrate, myocytes from young hearts are better able to use glucose, while cells from old hearts are better able to metabolize oleate.Supported by NIH AG030423

Accelerating hyperpolarized metabolic imaging of the heart by exploiting spatiotemporal correlations

Hyperpolarized (13)C-labeled pyruvate is a promising tool to investigate cardiac metabolism. It has been shown that changes in substrate metabolism occur following the induction of ischemia. To investigate the metabolic changes that are confined to spatial regions, high spatiotemporal resolution is required. The present work exploits both spatial and temporal correlations using k-t principal component analysis (PCA) to undersample the spatiotemporal domain, thereby speeding up data acquisition. A numerical model was implemented to investigate optimal acquisition and reconstruction parameters for pyruvate, lactate and bicarbonate maps of the heart. Subsequently, prospectively undersampled in vivo data on rat hearts were acquired using a combination of spectral-spatial signal excitation and a variable-density single-shot echo planar readout. Using five-fold k-t PCA, a spatial resolution of 1 × 1 mm(2) at a temporal resolution of 3 s was achieved.

The effect of green tea extract on fat oxidation at rest and during exercise: evidence of efficacy and proposed mechanisms.

Green tea is made from the leaves of the Camellia sinensis L plant, which is rich in polyphenol catechins and caffeine. There is increasing interest in the potential role of green tea extract (GTE) in fat metabolism and its influence on health and exercise performance. A number of studies have observed positive effects of GTE on fat metabolism at rest and during exercise, following both shorter and longer term intake. However, overall, the literature is inconclusive. The fact that not all studies observed effects may be related to differences in study designs, GTE bioavailability, and variation of the measurement (fat oxidation). In addition, the precise mechanisms of GTE in the human body that increase fat oxidation are unclear. The often-cited in vitro catechol-O-methyltransferase mechanism is used to explain the changes in substrate metabolism with little in vivo evidence to support it. Also, changes in expression of fat metabolism genes with longer term GTE intake have been implicated at rest and with exercise training, including the upregulation of fat metabolism enzyme gene expression in the skeletal muscle and downregulation of adipogenic genes in the liver. The exact molecular signaling that activates changes to fat metabolism gene expression is unclear but may be driven by PPAR-γ coactivator 1-α and PPARs. However, to date, evidence from human studies to support these adaptations is lacking. Clearly, more studies have to be performed to elucidate the effects of GTE on fat metabolism as well as improve our understanding of the underlying mechanisms.

Critical nutritional aspects in intensive care patients

Nutrition in the critically ill patients has always been a difficult task for the intensivist. Unlike normal subjects, various physiological and pathological aspects have to be taken into consideration before initiating the nutrition in this subset of patients. The associated morbidities in critically sick patient not only pose clinical difficulties to maintain a normal nutritional status but also create various limitations in selection of a particular nutrient. Various diseases commonly found in intensive care patients produces stress on the body and bring about changes in substrate metabolism thus leading to the deficiency of various nutrients. Numerous tools and methodologies are available nowadays to predict the assessment, screening, and monitoring of the nutritional status in critically ill patients. However, the nutritional status is a big decisive factor in predicting the outcome and malnutrition has been strongly associated with increased mortality and morbidity in these patients. The nutritional requirement also varies with regards to age, body mass index, co-morbid disease, duration in ICU, and many other factors and as such the calculation for nutritional supplementation has to be done strictly on an individual basis. In all these patients, it is also vital to achieve a strict glycemic control by using insulin so as to prevent any increase in morbidity and mortality. Enteral and parenteral nutritional controversies are as old as the concept of nutrition in Intensive Care Unit (ICU). Besides therapeutic merits, both enteral and parenteral nutrition are also associated with complications which can be prevented by set protocols as well as by education of nursing personnel involved in the care of critically ill. This article reviews all these aspects concerned with nutrition in critically ill patients so as to make an effort to build a comprehensive approach and strategies for designing the nutritional supplementation.

Prevention of Overweight/Obesity as a Strategy to Optimize Cardiovascular Health

The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). These risks associated with overweight/obesity are primarily related to the deposition of excess adiposity or body fatness. Weight loss, specifically loss of body fat, is associated with benefits in all of the obesity-related comorbidities, but, unfortunately, most weight loss interventions are associated with weight regain and are therefore not successful in the long term. It is for these reasons that efforts to prevent weight gain and overweight/obesity are necessary. This is especially important when one considers younger individuals, who have even more to lose as a consequence of a longer duration of excess adiposity. After a brief review of the epidemiology of obesity, this statement will make the case for the importance of weight gain prevention. This argument will first include a review of the complications of overweight and obesity in both adults and children, including the future CVD risks of obesity in early life. Energy balance dysregulation and adaptations to the weight-reduced state, favoring weight regain, will then be reviewed as further argument for the need for obesity prevention. This will be followed by a discussion on the goals and strategies for accomplishing the difficult task of the prevention of weight gain and obesity. ### Classification of Overweight and Obesity The body mass index (BMI) is the most widely used and accepted method for the assessment and classification of excess adiposity or body fatness. Overweight …

Mitochondrial targeted catalase suppresses invasive breast cancer in mice

BackgroundTreatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential.MethodsTransgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined.ResultsPyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects.ConclusionTargeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer.Please see related commentary article: http://www.biomedcentral.com/1741-7015/9/62

Is your brain to blame for weight regain?

Obesity is a serious and growing public health problem in the United States and the world. While weight loss is associated with significant benefits in obesity-related co-morbidities, successful long-term weight loss maintenance is extremely difficult. This limited success is primarily due to biologic mechanisms that clearly favor weight regain. The weight-reduced state is associated with not only reductions in energy expenditure and changes in substrate metabolism but also in increased energy intake. Measures of appetite (increased hunger, reduced satiety) clearly change with weight loss. These changes in appetite may be mediated by alterations of peripheral appetite-related signals, such as leptin and meal-related gut peptides, promoting energy intake. Furthermore, significant changes in the neuronal response to food-related cues in the weight-reduced state have also been shown, stressing the importance of the interactions between homeostatic and non-homeostatic regulation of energy intake. In summary, the weight-reduced state is clearly associated with a dysregulation of energy balance regulation, resulting in a milieu promoting weight regain, and thus being one of the major obstacles of “treating” obesity and reducing its comorbidities. This paper will review the adaptations in the central regulation of energy intake that occur after weight-loss or in the weight-reduce state in humans, including changes in peripheral appetite-related signals and neuroimaging studies examining the brain's response to weight loss.

Is your brain to blame for weight regain?

Obesity is a serious and growing public health problem in the United States and the world. While weight loss is associated with significant benefits in obesity-related co-morbidities, successful long-term weight loss maintenance is extremely difficult. This limited success is primarily due to biologic mechanisms that clearly favor weight regain. The weight-reduced state is associated with not only reductions in energy expenditure and changes in substrate metabolism but also in increased energy intake. Measures of appetite (increased hunger, reduced satiety) clearly change with weight loss. These changes in appetite may be mediated by alterations of peripheral appetite-related signals, such as leptin and meal-related gut peptides, promoting energy intake. Furthermore, significant changes in the neuronal response to food-related cues in the weight-reduced state have also been shown, stressing the importance of the interactions between homeostatic and non-homeostatic regulation of energy intake. In summary, the weight-reduced state is clearly associated with a dysregulation of energy balance regulation, resulting in a milieu promoting weight regain, and thus being one of the major obstacles of treating obesity and reducing its comorbidities. This paper will review the adaptations in the central regulation of energy intake that occur after weight-loss or in the weight-reduce state in humans, including changes in peripheral appetite-related signals and neuroimaging studies examining the brain's response to weight loss.