Effect of novel dietary supplement on metabolism in vitro and in vivo.

Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF) in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were measured hourly for 3 h post-ingestion. To investigate molecular effects, human rhabdomyosarcoma cells (RD) and mouse myocytes (C2C12) were treated with various doses of RF for various durations. RF enhanced energy expenditure and systolic blood pressure in human males without altering substrate utilization. In myocytes, RF enhanced metabolism, metabolic gene expression, and mitochondrial content suggesting RF may target common energetic pathways which control mitochondrial biogenesis. RF appears to increase metabolism immediately following ingestion, although it is unclear if RF provides benefits beyond those provided by caffeine alone. Additional research is needed to examine safety and efficacy for human weight loss.

trans-Cinnamaldehyde stimulates mitochondrial biogenesis through PGC-1α and PPARß/δ leading to enhanced GLUT4 expression.

Type 2 diabetes is characterized by insulin resistance and chronic hyperglycemia, and is increasing in incidence and severity. This work explored the effects of trans-cinnamaldehyde (CA) on carbohydrate metabolism, mitochondrial content, and related metabolic gene and protein expression in cultured myotubes treated with various concentrations of CA for up to 24 h. CA treatment increased myotube myocyte enhancer factor 2 (MEF2) along with glucose transporter 4 (GLUT4) content. CA treatment also significantly increased expression of markers of improved oxidative metabolism including 5' adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), cytochrome c (CytC), as well as peroxisome proliferator-activated receptor α (PPARα) and PPARß/δ. Despite increased expression of proteins associated with improved oxidative metabolism and glucose uptake, CA-treated myotubes exhibited significantly reduced oxidative metabolism compared with controlled cells. Additionally, CA treatment increased markers of glucose-mediated lipid biosynthesis without elevated PPARγ and sterol receptor element binding protein 1c (SREBP-1c) expression. The ability of CA to stimulate mitochondrial biogenesis and GLUT4 expression suggests CA may offer possible benefits for metabolic disease. However, increases in markers of fatty acid synthesis with simultaneously reduced oxidative metabolism suggest CA may have counterproductive effects for metabolic disease, warranting a need for further investigation.

Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism.

Exercise offers several benefits for health, including increased lean body mass and heightened energy expenditure, which may be partially attributable to secretory factors known as myokines. Irisin, a recently identified myokine, was shown to increase metabolic rate and mitochondrial content in both myocytes and adipocytes; however, the mechanism(s) of action still remain largely unexplained. This work investigated if irisin functions by acting as an inflammatory myokine leading to cellular stress and energy expenditure. C2C12 myotubes were treated with various concentrations of irisin, TNFα, or IL6 for various durations. Glycolytic and oxidative metabolism, as well as mitochondrial uncoupling, were quantified by measurement of acidification and oxygen consumption, respectively. Metabolic gene and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting, respectively. Mitochondrial content was assessed by fluorescent imaging. NFκB activity was assessed using an NFκB GFP-linked reporter system. Consistent with previous findings, irisin significantly increased expression of several genes including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) leading to increased mitochondrial content and oxygen consumption. Despite some similarities between TNFα and irisin treatment, irisin failed to activate the NFκB pathway like TNFα, suggesting that irisin may not act as an inflammatory signal. Irisin has several effects on myotube metabolism which appear to be dependent on substrate availability; however, the precise mechanism(s) by which irisin functions in skeletal muscle remain unclear. Our observations support the hypothesis that irisin does not function through inflammatory NFκB activation like other myokines (such as TNFα).

Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet.

Increased meal frequency (MF) may be associated with improvements in blood markers of health and body composition during weight loss; however, this claim has not been validated. The purpose of the study was to determine if either a 2-meal (2 MF) or 6-meal frequency (6 MF) regimen can improve body composition and blood-based markers of health while consuming a portion-controlled equihypocaloric diet. Eleven (N=11) obese women (52 ± 7 years, 101.7 ± 22.6 kg, 39.1 ± 7.6 kg/m(2)) were randomized into treatment condition (2 MF or 6 MF) for 2 weeks, completed a 2-week washout, and alternated treatment conditions. In pre/post fashion, changes in body composition, glucose, insulin, and lipid components were measured in response to a test meal. Body mass was successfully lost (P ≤ .05) under both feeding regimens (2 MF: -2.8 ± 1.5 vs 6 MF: -1.9 ± 1.5 kg). Altering MF did not impact glucose, insulin, total cholesterol, or low-density lipoprotein cholesterol (P>.05). On average, fat-free mass (FFM) decreased by -3.3% ± 2.6% following the 2 MF condition and, on average, increased by 1.2% ± 1.7% following the 6 MF condition (P ≤ .05). Fasting high-density lipoprotein cholesterol (HDL-C) percentage increased during the 2 MF condition; this was significantly greater than that in the 6 MF condition (1.3% ± 12.2% vs 0.12% ± 10.3%) (P ≤ .05). Overall, reductions in MF (2 MF) were associated with improved HDL-C levels; but the clinical significance is not clear. Alternatively, increased MF (6 MF) did appear to favorably preserve FFM during weight loss. In conclusion, caloric restriction was effective in reducing body mass and attenuating FFM changes in body composition; however, glucose, insulin, and lipid metabolism had no significant differences between MF.

Effect of post-exercise caffeine and green coffee bean extract consumption on blood glucose and insulin concentrations.

OBJECTIVE: The aim of this study was to investigate the effects of ingesting caffeine and green coffee bean extract on blood glucose and insulin concentrations during a post-exercise oral glucose tolerance test. METHODS: Ten male cyclists (age: 26 ± 5 y; height: 179.9 ± 5.4 cm; weight: 77.6 ± 13.3 kg; body mass index: 24 ± 4.3 kg/m(2); VO2 peak: 55.9 ± 8.4 mL·kg·min(-1)) participated in this study. In a randomized order, each participant completed three 30-min bouts of cycling at 60% of peak power output. Immediately after exercise, each participant consumed 75 g of dextrose with either 5 mg/kg body weight of caffeine, 10 mg/kg of green coffee bean extract (5 mg/kg chlorogenic acid), or placebo. Venous blood samples were collected immediately before and after exercise during completion of the oral glucose tolerance test. RESULTS: No significant time × treatment effects for blood glucose and insulin were found. Two-h glucose and insulin area under the curve values, respectively, for the caffeine (658 ± 74 mmol/L and 30,005 ± 13,304 pmol/L), green coffee bean extract (637 ± 100 mmol/L and 31,965 ± 23,586 pmol/L), and placebo (661 ± 77 mmol/L and 27,020 ± 12,339 pmol/L) trials were not significantly different (P > 0.05). CONCLUSION: Caffeine and green coffee bean extract did not significantly alter postexercise blood glucose and insulin concentrations when compared with a placebo. More human research is needed to determine the impact of these combined nutritional treatments and exercise on changes in blood glucose and insulin.

Dietary stimulators of GLUT4 expression and translocation in skeletal muscle: a mini-review.

Chronic insulin resistance can lead to type II diabetes mellitus, which is also directly influenced by an individual's genetics as well as their lifestyle. Under normal circumstances, insulin facilitates glucose uptake in skeletal muscle and adipose tissue by stimulating glucose transporter 4 (GLUT4) translocation and activity. GLUT4 activity is directly correlated with the ability to clear elevated blood glucose and insulin sensitivity. In diabetes, energy excess and prolonged hyperinsulinemia suppress muscle and adipose response to insulin, in part through reduced GLUT4 membrane levels. This work uniquely describes much of the experimental data demonstrating the effects of various dietary components on GLUT4 expression and translocation in skeletal muscle. These observations implicate several individual dietary chemicals as potential adjuvant therapies in the maintenance of diabetes and insulin resistance.

NAFLD Susceptibility Genes and their Association with Type 2 Diabetes and Obesity in a New Mexico Population.

OBJECTIVE: Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). One purpose of this study was to determine the frequencies of NAFLD susceptibility SNPs in a non-Hispanic white and Hispanic population who attended a clinic in northeast Albuquerque, NM. Another goal was to determine associations with selected indicators in this New Mexican population. METHODS: This cohort study involving 168 volunteer subjects in the NM population (88 non-Hispanic whites, 63 Hispanics, 4 Native Americans, 11 Asian Americans, 2 unreported ethnicity). Eight SNPs within 6 NAFLD susceptibility genes including PNPLA3 (rs738409), LYPLAL1 (rs12137855), APOC3 (rs2854116, rs2854117), GCKR (rs780094, rs741038), FABP2 (rs1799883), PEMT (rs7946) were analyzed by genotyping using the TaqMan genotyping assay (Applied Biosystems, Foster City, CA). Statistical analyses were carried out using statistical package SAS 9.3. RESULTS: The NAFLD allele frequencies were similar in non-Hispanic whites and Hispanics except for PNPLA3 (rs738409), FABP2 (rs1799883), and PEMT (rs7946). Eight SNPs in 5 NAFLD susceptibility genes were significantly associated OR marginally associated with selected indicators for NAFLD, metabolic syndrome, overweight, obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia. No SNPs were significantly associated with the same indicator in both the non-Hispanic white and Hispanic groups. CONCLUSIONS: In this population of non-Hispanic whites and Hispanics, there were only heterozygotes for the APOC3 derived alle le whereas for all other genes tested, both heterozygotes and homozygotes were found. Associations of alleles with indicators of chronic disease were different in non-Hispanic whites compared to Hispanics.

Effects of commercially available dietary supplements on resting energy expenditure: a brief report.

Commercially available dietary products advertised to promote weight loss are an underresearched but heavily purchased commodity in the United States. Despite only limited evidence, interest in dietary supplements continues to increase. This work uniquely summarizes the current evidence evaluating the efficacy of several over-the-counter thermogenic products for their effects on resting energy expenditure. Currently, there is some evidence suggesting dietary products containing select ingredients can increase energy expenditure in healthy young people immediately following consumption (within 6 hours). It is unclear if supplement-induced increases in metabolic rate provide additional benefit beyond that provided by dietary constituents that contain similar ingredients. It is also unclear if dietary supplements are effective for weight loss in humans.

Dietary stimulators of the PGC-1 superfamily and mitochondrial biosynthesis in skeletal muscle. A mini-review.

Mitochondrial dysfunction has been linked to many diseases including metabolic diseases such as diabetes. Peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) is a superfamily of transcriptional co-activators which are important precursors to mitochondrial biosynthesis found in most cells including skeletal muscle. The PGC-1 superfamily consists of three variants all of which are directly involved in controlling metabolic gene expression including those regulating fatty acid oxidation and mitochondrial proteins. In contrast to previous reviews on PGC-1, this mini-review summarizes the current knowledge of many known dietary stimulators of PGC-1 and the subsequent mitochondrial biosynthesis with associated metabolic benefit in skeletal muscle.

Potential role of meal frequency as a strategy for weight loss and health in overweight or obese adults.

Improved dietary strategies for weight loss are necessary to decrease metabolic disease risk in overweight or obese adults. Varying meal frequency (MF; i.e., increasing or decreasing eating occasions beyond the traditional pattern of three meals daily) has been thought to have an influence on body weight regulation, hunger control, and blood markers of health. It is common practice for weight management clinicians to recommend increasing MF as a strategy for weight management and to improve metabolic parameters. However, limited research exists investigating the effect of MF during controlled hypocaloric dietary interventions. Furthermore, MF literature often speculates with regard to efficacy of MF treatments based on research using normal weight, overweight/obese, or some combination, where much diversity exists within these various populations. In this review, we suggest that normal-weight and overweight/obese populations, as well as free-living versus investigator-controlled research trials, should be studied independently. Therefore, the objective of the present review is to survey the literature to assess whether the alteration of MF influences body weight regulation, hunger control, and/or blood markers of health in overweight/obese participants undergoing a controlled hypocaloric diet to induce weight loss. Findings of this review indicate that there is uncertainty in the literature when interpreting the optimal MF for obesity treatment, where reduced MF may even show more favorable lipid profiles in obese individuals compared with increased MF. Furthermore, the simple relationship of comparing MF with body fatness or body mass index should also consider whether eating frequency is associated with other healthy factors (e.g., increased physical activity).