Oligofructose-Enriched Inulin Consumption Acutely Modifies Markers of Postexercise Appetite.

Enhancing the effectiveness of exercise for long-term body weight management and overall health benefits may be aided through complementary dietary strategies that help to control acute postexercise energy compensation. Inulin-type fructans (ITFs) have been shown to induce satiety through the modified secretion of appetite-regulating hormones. This study investigated the acute impact of oligofructose-enriched inulin (OI) consumption after exercise on objective and subjective measures of satiety and compensatory energy intake (EI). In a randomized crossover study, following the completion of a 45 min (65-70% VO2peak) evening exercise session, participants (BMI: 26.9 ± 3.5 kg/m2, Age: 26.8 ± 6.7 yrs) received one of two beverages: (1) sweetened milk (SM) or (2) sweetened milk + 20 g OI (SM+OI). Perceived measures of hunger were reduced in SM+OI relative to SM (p = 0.009). Within SM+OI, but not SM, plasma concentrations of GLP-1 and PYY were increased and acyl-ghrelin reduced from pre-exercise to postexercise. EI during the ad libitum breakfast in the morning postexercise tended to be lower in SM+OI (p = 0.087, d = 0.31). Gastrointestinal impacts of OI were apparent with increased ratings of flatulence (p = 0.026, d = 0.57) in participants the morning after the exercise session. Overall, the ingestion of a single dose of OI after an exercise session appears to induce subtle reductions in appetite, although the impact of these changes on acute and prolonged EI remains unclear.

Influence of postexercise fasting on hunger and satiety in adults.

Research demonstrates that exercise acutely reduces appetite by stimulating the secretion of gut-derived satiety hormones. Currently there is a paucity of research examining the impact of postexercise nutrient intake on appetite regulation. The objective of this study was to examine how postexercise fasting versus feeding impacts the postexercise appetite response. In a randomized crossover intervention, 14 participants (body mass index: 26.9 ± 3.5 kg·m-2; age: 26.8 ± 6.7 years) received 1 of 2 recovery beverages: (i) water control (FAST) or (ii) sweetened-milk (FED) after completing a 45-min (65%-70% peak oxygen uptake) evening exercise session (∼1900 h). Energy intake was assessed through a fasted ad libitum breakfast meal and 3-day food diaries. Perceived appetite was assessed using visual analogue scales. Appetite-regulating hormones glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and acyl-ghrelin were assessed pre-exercise, 1 h after exercise, and the morning following exercise. FAST increased subjective hunger compared with FED (P < 0.05). PYY and GLP-1 after exercise were decreased and acyl-ghrelin was increased in FAST, with these differences disappearing the day after exercise (P < 0.05). Ad libitum energy intake at breakfast the following morning did not differ between trials. Overall, in the absence of postexercise macronutrient consumption, there was a pronounced increase in objective and subjective appetite after exercise. The orexigenic effects of postexercise fasting, however, were not observed the morning following exercise. Novelty Postexercise fasting leads to reduced GLP-1 and PYY and increased hunger. Reduced GLP-1 and PYY after exercise is blunted by postexercise nutrient intake. Energy intake the day after exercise is not influenced by postexercise fasting.

Exogenous Ketones Lower Post-exercise Acyl-Ghrelin and GLP-1 but Do Not Impact Ad libitum Energy Intake.

Ketosis and exercise are both associated with alterations in perceived appetite and modification of appetite-regulating hormones. This study utilized a ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) to examine the impact of elevated ketone body D-ß-hydroxybutyrate (ßHB) during and after a bout of exercise on appetite-related hormones, appetite perception, and ad libitum energy intake over a 2 h post-exercise period. In a randomized crossover trial, 13 healthy males and females (age: 23.6 ± 2.4 years; body mass index: 25.7 ± 3.2 kg·m-2) completed an exercise session @ 70% VO2peak for 60 min on a cycling ergometer and consumed either: (1) Ketone monoester (KET) (0.5 g·kg-1 pre-exercise + 0.25 g·kg-1 post-exercise); or (2) isocaloric dextrose control (DEX). Transient ketonaemia was achieved with ßHB concentrations reaching 5.0 mM (range 4.1-6.1 mM) during the post-exercise period. Relative to the dextrose condition, acyl-ghrelin (P = 0.002) and glucagon-like peptide-1 (P = 0.038) were both reduced by acute ketosis immediately following exercise. AUC for acyl-ghrelin was lower in KET compared to DEX (P = 0.001), however there were no differences in AUC for GLP-1 (P = 0.221) or PYY (P = 0.654). Perceived appetite (hunger, P = 0.388; satisfaction, P = 0.082; prospective food consumption, P = 0.254; fullness, P = 0.282) and 2 h post-exercise ad libitum energy intake (P = 0.488) were not altered by exogenous ketosis. Although KE modifies homeostatic regulators of appetite, it does not appear that KE acutely alters energy intake during the post-exercise period in healthy adults.

Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity.

Obesity, and associated metabolic syndrome, have been identified as primary risk factors for the development of knee osteoarthritis (OA), representing nearly 60% of the OA patient population. In this study, we sought to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions, on the development of metabolic knee osteoarthritis in a high-fat/high-sucrose (HFS) diet-induced rat model of obesity. Twelve-week-old male Sprague-Dawley rats were randomized into five groups: a non-exercising control group fed a standard chow diet, a non-exercising group fed a HFS diet, a non-exercising group fed a HFS diet combined with prebiotic fibre supplement, an exercise group fed a HFS diet, and an exercise group fed a HFS diet combined with prebiotic fibre supplement. Outcome measures included knee joint damage, percent body fat, insulin sensitivity, serum lipid profile, serum endotoxin, serum and synovial fluid cytokines and adipokines, and cecal microbiota. Prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions completely prevented knee joint damage that is otherwise observed in this rat model of obesity. Prevention of knee damage was associated with a normalization of insulin resistance, leptin levels, dyslipidemia, gut microbiota, and endotoxemia in the HFS-fed rats.

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.

Comparison of Glucose and Satiety Hormone Response to Oral Glucose vs. Two Mixed-Nutrient Meals in Rats.

The obesity epidemic is driving interest in identifying strategies that enhance appetite control by altering the secretion of hormones that regulate satiety and food intake. An appropriate nutrient stimulus, such as a meal or oral nutrient solution, is needed to elicit the secretion of satiety hormones in order to evaluate the impact of dietary and other interventions. Our objective was to compare the effects of oral glucose vs. mixed nutrients on plasma concentrations of glucose and appetite-regulating hormones to determine the most appropriate oral nutrient challenge to trigger robust hormone secretion. A 120 min oral glucose tolerance test (OGTT) was compared with two meal tolerance tests (MTT) of differing formulation to evaluate glucose and satiety hormone responses. Following overnight feed deprivation, male Sprague-Dawley rats were given one of three oral gavages with equal carbohydrate content (2 g CHO/kg) in the form of: (1) Dextrose, (2) Ensure®, or (3) Mixed Meal. A fourth group was given saline as a control. Blood was collected via tail snip and analyzed for glucose, insulin, GLP-1, GIP, PYY, amylin, leptin, and ghrelin. Dextrose resulted in the highest blood glucose at T15 (P = 0.014), while the mixed meal was significantly higher than saline from T30-T120 (P < 0.05). Insulin was higher at T15 with dextrose compared to saline (P = 0.031) and Ensure® (P = 0.033). GLP-1 tAUC was significantly higher with dextrose compared to mixed meal (P = 0.04) while GIP tAUC was higher with dextrose and mixed meal compared to saline (P < 0.05). Changes in tAUC for insulin, amylin, leptin, ghrelin, and PYY did not reach significance. Based on these findings, dextrose appears to provide a robust acute glycemic and hormone response and is therefore likely an appropriate oral solution to reproducibly test the impact of various dietary, surgical, or pharmacological interventions on glucose and satiety hormone response.

Potential Impact of Metabolic and Gut Microbial Response to Pregnancy and Lactation in Lean and Diet-Induced Obese Rats on Offspring Obesity Risk.

SCOPE: Maternal obesity programs metabolic dysfunction in offspring, increasing their susceptibility to obesity and metabolic diseases in later life. Moreover, pregnancy and lactation are associated with many metabolic adaptations, yet it is unclear how diet-induced maternal obesity may interrupt these processes. METHODS AND RESULTS: 1 H NMR serum metabolomics analysis was performed on samples collected pre-pregnancy and in pregnant and lactating lean and high fat/sucrose (HFS) diet-induced obese Sprague-Dawley rats to identify maternal metabolic pathways associated with developmental programming of offspring obesity. Gut microbial composition was assessed using qPCR. Offspring of HFS dams had nearly 40% higher adiposity at weaning compared to offspring of lean dams. While pregnancy and lactation were associated with distinct maternal metabolic changes common to both lean and obese dams, we identified several metabolic differences, potentially implicating dysregulated one-carbon and mammary gland metabolism in the metabolic programming of obesity. Gut microbial composition was significantly altered with obesity, and both gestation and lactation were accompanied by changes in gut microbiota. CONCLUSION: Diet-induced maternal obesity and consumption of an obesogenic maternal diet results in differential metabolic and gut microbial adaptations to pregnancy and lactation; these maladaptations may be directly involved in maternal programming of offspring susceptibility to obesity.

Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder.

BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.

Improvement in adiposity with oligofructose is modified by antibiotics in obese rats.

Given the intimate link between gut microbiota and host physiology, there is growing interest in understanding the mechanisms by which diet influences gut microbiota and affects human metabolic health. Using antibiotics and the prebiotic oligofructose, which has been shown to counteract excess fat mass, we explored the gut microbiota-dependent effects of oligofructose on body composition and host metabolism. Diet-induced obese male Sprague Dawley rats, fed a background high-fat/sucrose diet, were randomized to one of the following diets for 6 wk: 1) high-energy control; 2) 10% oligofructose; 3) ampicillin; 4) ampicillin + 10% oligofructose; 5) ampicillin/neomycin; or 6) ampicillin/neomycin + 10% oligofructose. Combining oligofructose with ampicillin treatment blunted the decrease in adiposity seen with oligofructose. Although ampicillin did not affect total bacteria, ampicillin impeded oligofructose-induced increases in Bifidobacterium and Lactobacillus In contrast, the combination of ampicillin and neomycin reduced total bacteria but did not abrogate the oligofructose-induced decrease in adiposity. Oligofructose-mediated effects on host adiposity and metabolic health appear to be in part dependent on the presence of specific microbial species within the gut.-Bomhof, M. R., Paul, H. A., Geuking, M. B., Eller, L. K., Reimer, R. A. Improvement in adiposity with oligofructose is modified by antibiotics in obese rats.

Metabolomic Modeling To Monitor Host Responsiveness to Gut Microbiota Manipulation in the BTBR(T+tf/j) Mouse.

The microbiota, the entirety of microorganisms residing in the gut, is increasingly recognized as an environmental factor in the maintenance of health and the development of disease. The objective of this analysis was to model in vivo interactions between gut microbiota and both serum and liver metabolites. Different genotypic models (C57BL/6 and BTBR(T+tf/j) mice) were studied in combination with significant dietary manipulations (chow vs ketogenic diets) to perturb the gut microbiota. Diet rather than genotype was the primary driver of microbial changes, with the ketogenic diet diminishing total bacterial levels. Fecal but not cecal microbiota profiles were associated with the serum and liver metabolomes. Modeling metabolome-microbiota interactions showed fecal Clostridium leptum to have the greatest impact on host metabolism, significantly correlating with 10 circulating metabolites, including 5 metabolites that did not correlate with any other microbes. C. leptum correlated negatively with serum ketones and positively with glucose and glutamine. Interestingly, microbial groups most strongly correlated with host metabolism were those modulating gut barrier function, the primary site of microbe-host interactions. These results show very robust relationships and provide a basis for future work wherein the compositional and functional associations of the microbiome can be modeled in the context of the metabolome.

Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol.

BACKGROUND: Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. METHODS/DESIGN: In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. DISCUSSION: There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.

Exercise training modifies gut microbiota in normal and diabetic mice.

Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics.

Epidemiological data confirms a strong negative association between regular coffee consumption and the prevalence of type 2 diabetes. Coffee is initially absorbed in the stomach and small intestine but is further fermented in the colon by gut microbiota. The bioavailability, production and biological activity of coffee polyphenols is modulated, in part, by gut microbiota. The purpose of this study was to determine if chronic coffee consumption could mitigate negative gut microbiota and metabolomic profile changes induced by a high-fat diet. Male Sprague-Dawley rats were randomized to chow (12% kcal fat) or high-fat (60% kcal fat) diet. Each group was further divided into water or caffeinated coffee for 10 weeks. Coffee consumption in high-fat-fed rats was associated with decreased body weight, adiposity, liver triglycerides and energy intake. Despite a more favorable body composition, rats displayed profound systemic insulin resistance, likely due to caffeine. Coffee consumption attenuated the increase in Firmicutes (F)-to-Bacteroidetes (B) ratio and Clostridium Cluster XI normally associated with high-fat feeding but also resulted in augmented levels of Enterobacteria. In the serum metabolome, coffee had a distinct impact, increasing levels of aromatic and circulating short-chain fatty acids while lowering levels of branched-chain amino acids. In summary, coffee consumption is able to alter gut microbiota in high-fat-fed rats although the role of these changes in reducing diabetes risk is unclear given the increased insulin resistance observed with coffee in this study.

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats.

OBJECTIVE: Prebiotics and probiotics may be able to modify an obesity-associated gut microbiota. The aim of this study was to examine the individual and combined effects of the prebiotic oligofructose (OFS) and the probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on gut microbiota and host metabolism in obese rats. METHODS: Adult male, diet-induced obese Sprague Dawley rats were randomized to: (1) Control (C); (2) 10% OFS; (3) BB-12; (4) OFS + BB-12 for 8 weeks (n = 9-10 rats/group). Body composition, glycemia, gut permeability, satiety hormones, cytokines, and gut microbiota were examined. RESULTS: Prebiotic, but not probiotic reduced energy intake, weight gain, and fat mass (P < 0.01). OFS, BB-12, and the combined OFS + BB-12 improved glycemia (P < 0.05). Individually, OFS and BB-12 reduced insulin levels (P < 0.05). Portal GLP-1 was increased with OFS, whereas probiotic increased GLP-2 (P < 0.05). There was a marked increase in bifidobacteria and lactobacilli (P < 0.01) with OFS that was not observed with probiotic alone. CONCLUSIONS: The impact of prebiotic intake on body composition and gut microbiota was of greater magnitude than the probiotic BB-12. Despite this, an improvement in glucose AUC with both prebiotic or probiotic demonstrates the beneficial role of each of these "biotic" agents in glycemic control.

Muscle-specific differences in the response of mitochondrial proteins to beta-GPA feeding: an evaluation of potential mechanisms.

Beta-Guanadinopropionic acid (beta-GPA) feeding leads to reductions in skeletal muscle phosphagen concentrations and has been used as a tool with which to study the effects of energy charge on skeletal muscle metabolism. Supplementing standard rodent diets with beta-GPA leads to increases in mitochondrial enzyme content in fast but not slow-twitch muscles from male rats. Given this apparent discrepancy between muscle types we used beta-GPA feeding as a model to study signaling pathways involved in mitochondrial biogenesis. We hypothesized that beta-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle. Despite similar reductions in high-energy phosphate concentrations, 6 wk of beta-GPA feeding led to increases in mitochondrial proteins in triceps but not soleus muscles. Differences in the response of mitochondrial proteins to beta-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARgamma coactivator (PGC)-1alpha and -1beta. The protein content and expression of the nuclear corepressor RIP140 was reduced in triceps but not soleus muscle. Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1alpha and -1beta in both soleus and triceps muscles. The lack of an effect of beta-GPA feeding on mitochondrial proteins in the soleus muscles could be related to a fiber type-specific effect of beta-GPA on RIP140 protein content.

Exercise and adrenaline increase PGC-1{alpha} mRNA expression in rat adipose tissue.

The purpose of the present investigation was to explore the effects of exercise and adrenaline on the mRNA expression of PGC-1alpha, a master regulator of mitochondrial biogenesis, in rat abdominal adipose tissue. We hypothesized that (1) exercise training would increase PGC-1alpha mRNA expression in association with increases in mitochondrial marker enzymes, (2) adrenaline would increase PGC-1alpha mRNA expression and (3) the effect of exercise on PGC-1alpha mRNA expression in white adipose tissue would be attenuated by a beta-blocker. Two hours of daily swim training for 4 weeks led to increases in mitochondrial marker proteins and PGC-1alpha mRNA expression in epididymal and retroperitoneal fat depots. Additionally, a single 2 h bout of exercise led to increases in PGC-1alpha mRNA expression immediately following exercise cessation. Adrenaline treatment of adipose tissue organ cultures led to dose-dependent increases in PGC-1alpha mRNA expression. A supra-physiological concentration of adrenaline increased PGC-1alpha mRNA expression in epididymal but not retroperitoneal adipose tissue. beta-Blockade attenuated the effects of an acute bout of exercise on PGC-1alpha mRNA expression in epididymal but not retroperitoneal fat pads. In summary, this is the first investigation to demonstrate that exercise training, an acute bout of exercise and adrenaline all increase PGC-1alpha mRNA expression in rat white adipose tissue. Furthermore it would appear that increases in circulating catecholamine levels may be one potential mechanism mediating exercise induced increases in PGC-1alpha mRNA expression in rat abdominal adipose tissue.