The dynamic life of the glycogen granule.

Glycogen, the primary storage form of glucose, is a rapid and accessible form of energy that can be supplied to tissues on demand. Each glycogen granule, or "glycosome," is considered an independent metabolic unit composed of a highly branched polysaccharide and various proteins involved in its metabolism. In this Minireview, we review the literature to follow the dynamic life of a glycogen granule in a multicompartmentalized system, i.e. the cell, and how and where glycogen granules appear and the factors governing its degradation. A better understanding of the importance of cellular compartmentalization as a regulator of glycogen metabolism is needed to unravel its role in brain energetics.

Nutra-ergonomics: influence of nutrition on physical employment standards and the health of workers.

The importance of ergonomics across several scientific domains, including biomechanics, psychology, sociology, and physiology, have been extensively explored. However, the role of other factors that may influence the health and productivity of workers, such as nutrition, is generally overlooked. Nutra-ergonomics describes the interface between workers, their work environment, and performance in relation to their nutritional status. It considers nutrition to be an integral part of a safe and productive workplace that encompasses physical and mental health as well as the long-term wellbeing of workers. This review explores the knowledge, awareness, and common practices of nutrition, hydration, stimulants, and fortified product use employed prior to physical employment standards testing and within the workplace. The influence of these nutra-ergonomic strategies on physical employment standards, worker safety, and performance will be examined. Further, the roles, responsibilities, and implications for the applicant, worker, and the employer will be discussed within the context of nutra-ergonomics, with reference to the provision and sustainability of an environment conducive to optimize worker health and wellbeing. Beyond physical employment standards, workplace productivity, and performance, the influence of extended or chronic desynchronization (irregular or shift work) in the work schedule on metabolism and long-term health, including risk of developing chronic and complex diseases, is discussed. Finally, practical nutra-ergonomic strategies and recommendations for the applicant, worker, and employer alike will be provided to enhance the short- and long-term safety, performance, health, and wellbeing of workers.

Towards best practice in physical and physiological employment standards.

While the scope of the term physical employment standards is wide, the principal focus of this paper is on standards related to physiological evaluation of readiness for work. Common applications of such employment standards for work are in public safety and emergency response occupations (e.g., police, firefighting, military), and there is an ever-present need to maximize the scientific quality of this research. Historically, most of these occupations are male-dominated, which leads to potential sex bias during physical demands analysis and determining performance thresholds. It is often assumed that older workers advance to positions with lower physical demand. However, this is not always true, which raises concerns about the long-term maintenance of physiological readiness. Traditionally, little attention has been paid to the inevitable margin of uncertainty that exists around cut-scores. Establishing confidence intervals around the cut-score can reduce for this uncertainty. It may also be necessary to consider the effects of practise and biological variability on test scores. Most tests of readiness for work are conducted under near perfect conditions, while many emergency responses take place under far more demanding and unpredictable conditions. The potential impact of protective clothing, respiratory protection, load carriage, environmental conditions, nutrition, fatigue, sensory deprivation, and stress should also be considered when evaluating readiness for work. In this paper, we seek to establish uniformity in terminology in this field, identify key areas of concern, provide recommendations to improve both scientific and professional practice, and identify priorities for future research.

Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle.

Resistant starch intake at breakfast affects postprandial responses in type 2 diabetics and enhances the glucose-dependent insulinotropic polypeptide--insulin relationship following a second meal.

Resistant starch (RS) consumption can modulate postprandial metabolic responses, but its effects on carbohydrate (CHO) handling in type 2 diabetics (T2D) are unclear. It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal, regardless of the amount of available CHO, and that in association with incretins, the effects would carry over to a 2nd meal. Using a randomized crossover design, 12 T2D ingested four different bagel treatments (their 1st meal) determined by available CHO and the weight or amount of bagel consumed: treatment A, without RS (50 g of available CHO); treatment B, with RS (same total CHO as in A); treatment C, with RS (same available CHO as in A); and treatment D, with the same RS as in B and available CHO as in A and C. A standard 2nd meal was ingested 3 h later. Following the first meal, B elicited a lower glucose incremental area under the curve (iAUC) than C (P < 0.05), D (P < 0.05), and A (trend; P = 0.07), lower insulin iAUC than A (P < 0.05) and C (P < 0.05), and lower glucose-dependent insulinotropic polypeptide (GIP) iAUC than A (P < 0.05). There was a positive correlation (P < 0.05) between GIP and insulin iAUCs after the 2nd meal, and C had a 3 times greater slope than the other treatments (r = 0.91, P < 0.001), yet lacked a significant concomitant improvement in glucose disposal. These results show that for the 1st meal, RS was effective when it replaced a portion of the available CHO, while ingesting more RS influenced the GIP-insulin axis following the 2nd meal.

Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women.

The effects of alkaloid caffeine on insulin sensitivity have been investigated primarily in men, and with a single caffeine dose most commonly of 5-6 mg·kg(-1) of body weight (BW). It is unknown if the effects of caffeine on glucose homeostasis are sex-specific and (or) dose-dependent. This study examined whether caffeine ingestion would disrupt glucose homeostasis in a dose-dependent or threshold manner. It also examined whether sex-specific responses to caffeine exist. It was hypothesized that women would have an exaggerated response to caffeine, and that caffeine would only impair glucose metabolism once a threshold was reached. Twenty-four healthy volunteers (12 males, 12 females) participated in 4 trials, in a crossover, randomized, and double-blind fashion. They ingested caffeine (1, 3, or 5 mg·kg(-1) of BW) or placebo followed, 1 h later, by a 2-h oral glucose tolerance test. Glucose, insulin, C-peptide area under the curve (AUC), and insulin sensitivity index data were fitted to a segmented linear model to determine dose-responses. There were no differences between sexes for any endpoints. Regression slopes were significantly different from zero (p < 0.05) for glucose, insulin, and C-peptide AUCs, with thresholds being no different from zero. Increasing caffeine consumption by 1 mg·kg(-1) of BW increased insulin and C-peptide AUCs by 5.8% and 8.7%, respectively. Despite this exaggerated insulin response, glucose AUC increased by 11.2 mmol per 120 min·L(-1) for each mg·kg(-1) BW consumed. These results showed that caffeine ingestion disrupted insulin sensitivity in a dose-dependent fashion beginning at very low doses (0-1 mg·kg(-1) BW) in both healthy men and women.

Vaccenic acid in serum triglycerides is associated with markers of insulin resistance in men.

Serum triglyceride levels are associated with metabolic disorders; however, it remains unclear whether the fatty acid (FA) composition of triglycerides is also changed. Although there were no differences in circulating triglyceride levels between normoglycaemic-normoinsulinaemic and hyperglycaemic-hyperinsulinaemic men, inspection of individual FA revealed that vaccenic acid was enriched with hyperglycaemia-hyperinsulinaemia. Moreover, vaccenic acid levels were positively correlated with insulin and HOMA-IR. This reinforces that examination of individual FA in the context of insulin resistance is warranted.

The acute impact of ingestion of sourdough and whole-grain breads on blood glucose, insulin, and incretins in overweight and obese men.

Consumption of whole-grain and sourdough breads is associated with improved glucose homeostasis. We examined the impact of commercial breads on biomarkers of glucose homeostasis in subjects at risk for glucose intolerance. In a randomized, crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12-grain, sourdough, or white bread on different occasions, matched for available carbohydrate (50 g) in part 1 (n = 12) and bread mass (107 g) in part 2 (n = 11), and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were determined for 3 h. In part 1, glucose response for sprouted-grain was lower than 11-grain, sourdough, and white breads. Insulin area under the curve (AUC) for sourdough and white was lower than 11-grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all breads. In part 2, glucose and insulin AUC for sourdough was greater than 11-grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved glycemia by lowering glucose response and increasing GLP-1 response. In overweight and obese men, the glycemic response to sprouted grain bread was reduced in both parts 1 and 2 while the other whole-grain test breads did not improve metabolic responses in the acute postprandial state.

An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.

Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

Methylxanthines and human health: epidemiological and experimental evidence.

When considering methylxanthines and human health, it must be recognized that in many countries most caffeine is consumed as coffee. This is further confounded by the fact that coffee contains many bioactive substances in addition to caffeine; it is rich in phenols (quinides, chlorogenic acid, and lactones) and also has diterpenes (fatty acid esters), potassium, niacin, magnesium, and the vitamin B(3) precursor trigonelline. There is a paradox as consumption of either caffeine or caffeinated coffee results in a marked insulin resistance and yet habitual coffee consumption has repeatedly been reported to markedly reduce the risk for type 2 diabetes. There is strong evidence that caffeine reduces insulin sensitivity in skeletal muscle and this may be due to a combination of direct antagonism of A(1) receptors and indirectly ß-adrenergic stimulation as a result of increased sympathetic activity. Caffeine may also induce reduced hepatic glucose output. With the exception of bone mineral, there is little evidence that caffeine impacts negatively on other health issues. Coffee does not increase the risk of cardiovascular diseases or cancers and there is some evidence suggesting a positive relationship for the former and for some cancers, particularly hepatic cancer.

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial.

BACKGROUND: Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains. METHODS: This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the APOE gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (LIPC -514C>T, LIPC -250G>A) were considered. RESULTS: At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the APOE E3/E3 genotype, LDL-cholesterol (P = 0.02) increased in the NGI group (n = 7), and TAG (P = 0.03) and TAG:HDL-cholesterol (P = 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread. CONCLUSIONS: In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the APOE E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.

Exercise prior to fat ingestion lowers fasting and postprandial VLDL and decreases adipose tissue IL-6 and GIP receptor mRNA in hypertriacylglycerolemic men.

Fasting and postprandial triacylglycerol (TAG) concentrations are risk factors for cardiovascular disease. This study evaluated whether interleukin-6 (IL-6) and incretin hormones [gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) (active)] were associated with fasting and postprandial TAG in response to an oral lipid load, including very-low-density lipoprotein (VLDL) and chylomicron (CM) TAG, following one bout of exercise in nine men (age, 59 ± 2 years; body mass index, 34 ± 2 kg/m2; waist circumference, 113 ± 3 cm) with high fasting TAG (2.9 ± 0.2 mmol/L). Subjects completed two oral fat tolerance tests (OFTTs), randomized 1 week apart, that consisted of 1g fat/kg body weight emulsified lipids in the absence of carbohydrate and protein. Approximately 16 h prior to one OFTT, subjects completed 60 min of treadmill walking (estimated 55% VO2 peak; heart rate, 122 ± 4 beats/min). No exercise was performed on the day before the other OFTT. Fasted (0 h) and postprandial (1, 2, 3, 4, 5 and 6 h) blood samples were taken for analysis of TAG, IL-6 and incretins. Subcutaneous adipose tissue biopsies were taken at 0 and 6 h after OFTT ingestion for IL-6 and GIP receptor (GIPr) mRNA quantification. Exercise lowered fasting and postprandial TAG (P<.05) and VLDL TAG (P<.05), while postprandial CM TAG were similar in both OFTT trials (P>.05). Fasting and postprandial plasma IL-6, GIP and GLP-1 did not differ between rest and exercise OFTT trials (P>.05). Exercise reduced IL-6 and GIPr mRNA (P<.05) in adipose tissue. Our results suggest that the reduction in VLDL TAG following an acute bout of exercise is not associated with circulating IL-6 or incretin concentrations, despite reductions in the adipose tissue expression of IL-6 and GIPr.

Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males.

Caffeine and caffeinated coffee (CC) elicit acute insulin insensitivity when ingested before a carbohydrate load. The effects of CC on glucose tolerance and insulin sensitivity when co-ingested with a high carbohydrate meal and on postprandial metabolism of a subsequent (second) carbohydrate load have not been studied. In a randomised, crossover design, ten healthy males ingested either CC (5 mg caffeine/kg body weight), decaffeinated coffee (DC) or water (W; equal volume) co-ingested with a high glycaemic index cereal followed 3 h later by a 75 g oral glucose tolerance test. After the initial meal, insulin area under the curve (AUC) and insulin sensitivity index did not differ between treatments, although glucose AUC for CC (107 (sem 18) mmol/l x 3 h) and DC (74 (sem 15) mmol/l x 3 h) was greater than W ( - 0.2 (sem 29) mmol/l x 3 h, P < 0.05). After the second carbohydrate load, insulin AUC for CC was 49 % and 57 % greater (P < 0.01) than for DC and W, respectively. Despite the greater insulin response, glucose AUC for CC (217 (sem 24) mmol/l x 2 h) was greater than both DC (126 (sem 11) mmol/l x 2 h, P = 0.01) and W (55 (sem 34) mmol/l x 2 h, P < 0.001). Insulin sensitivity index after the second meal was lower after CC (8.2 (sem 0.9)) compared with both DC (12.4 (sem 1.2), P < 0.01) and W (13.4 (sem 1.4), P < 0.001). Co-ingestion of CC with one meal resulted in insulin insensitivity during the postprandial phase of a second meal in the absence of further CC ingestion. Thus, CC may play a role in daily glycaemic management.

Acute caffeine ingestion and glucose tolerance in women with or without gestational diabetes mellitus.

OBJECTIVE: Recent work showing that caffeine impairs glucose tolerance may be of particular concern in pregnancy because of a possible negative effect on fetal outcome. The current study sought to assess the effect of acute caffeine ingestion on glucose tolerance in women with or without gestational diabetes mellitus (GDM). METHODS: Nineteen women whose routine GDM test was negative (control) and eight women with an initial positive GDM screen completed two trials one week apart in a double-blind randomized crossover study. Following an overnight fast, subjects ingested caffeine (3 mg/kg pre-pregnancy body weight) or an identical-appearing placebo (gelatin) capsule and one hour later began a 75 g 2-hour oral glucose tolerance test. RESULTS: In the control group, caffeine did not significantly affect blood glucose, insulin, or C-peptide. In the GDM group, glucose area under the curve (AUC) was greater (P < 0.01), C-peptide AUC was greater (P < 0.05), and insulin sensitivity index was lower (18%, P < 0.05) after caffeine than after placebo. CONCLUSION: Caffeine impaired insulin sensitivity in women with GDM. Additional research regarding more specific dietary caffeine recommendations for women with GDM is warranted.

Glycogen: an overview of possible regulatory roles of the proteins associated with the granule.

While scientists have routinely measured muscle glycogen in many metabolic situations for over 4 decades, there is surprisingly little known regarding its regulation. In the past decade, considerable evidence has illustrated that the carbohydrate stores in muscle are not homogeneous, and it is very likely that metabolic pools exist or that each granule has independent regulation. The fundamental aspects appear to be associated with a complex set of proteins that associate with both the granule and each other in a dynamic fashion. Some of the proteins are enzymes and others play scaffolding roles. A number of the proteins can translocate, depending on the metabolic stimulus. These various processes appear to be the mechanisms that give the glycogen granule precise yet dynamic regulation. This may also allow the stores to serve as an important metabolic regulator of other metabolic events.

Fasting triacylglycerol status, but not polyunsaturated/saturated fatty acid ratio, influences the postprandial response to a series of oral fat tolerance tests.

Elevated postprandial lipemia is emerging as a risk factor for obesity-related chronic diseases, such as type 2 diabetes and cardiovascular disease, and is associated with alterations in several metabolic biomarkers of disease. Our goal was to examine the effects of specific polyunsaturated/saturated fatty acid (P/S) ratios on postprandial triacylglycerol (TAG) concentrations and metabolic biomarkers in men with different fasting TAG concentrations through a series of oral fat tolerance tests (OFTT) consisting solely of emulsified lipid. Otherwise healthy men with high (>1.69 mmol/L) fasting TAG (HTAG, n=8) and low fasting TAG (LTAG, n=8) underwent three OFTTs with specific P/S ratios of 0.2, 1.0 and 2.0, respectively, and a total lipid load of 1 g/kg subject body mass. All subjects received each treatment separated by at least 1 week. Postprandial plasma TAG fatty acid composition reflected fatty acids present in the OFTT. All other metabolic responses were independent of the P/S ratio ingested. An accelerated increase in postprandial TAGs was observed in HTAG compared to LTAG. Interleukin (IL)-6 and soluble intercellular adhesion molecule (sICAM)-1 were significantly elevated in HTAG at baseline (P<.05). IL-6 increased significantly following each OFTT (P<.05) in both groups. Postprandial glucose and CRP were significantly exaggerated (P<.05) in HTAG. Overall, HTAG subjects had an accelerated postprandial TAG response and increased concentrations of several inflammatory markers following an OFTT, in the absence of an insulin response. However, P/S ratio had no influence on postprandial lipid and inflammatory parameters.

The acute impact of ingestion of breads of varying composition on blood glucose, insulin and incretins following first and second meals.

Structural characteristics and baking conditions influence the metabolic responses to carbohydrate-containing foods. We hypothesized that consumption of whole wheat or sourdough breads would have a favourable effect on biomarkers of glucose homeostasis after first and second meals, compared with those for white bread. Ten overweight volunteers consumed 50 g available carbohydrate of each of the four breads (white, whole wheat, sourdough, whole wheat barley) followed 3 h later by a standard second meal. Blood was sampled for 3 h following bread ingestion and a further 2 h after the second meal for determination of glucose, insulin, paracetamol (indirect marker of gastric emptying), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Glucose and GLP-1 responses to sourdough bread were lower (P < 0.05) than whole wheat and whole wheat barley breads. Glucose area under the curve (AUC) for sourdough bread was lower than those for whole wheat (P < 0.005) and whole wheat barley (P < 0.03) breads for the entire study. GIP AUC after sourdough bread ingestion was lower compared to white (P < 0.004) and whole wheat barley (P < 0.002) breads following the second meal. There were no significant differences in insulin and paracetamol concentrations among the test breads. Ultra-fine grind whole wheat breads did not result in postprandial responses that were lower than those of white bread, but sourdough bread resulted in lower glucose and GLP-1 responses compared to those of these whole wheat breads following both meals.

Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

Caffeine, an adenosine receptor antagonist, has been studied for decades as a putative ergogenic aid. In the past 2 decades, the information has overwhelmingly demonstrated that it indeed is a powerful ergogenic aid, and frequently theories have been proposed that this is due to alterations in fat and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically important. The few studies examining human muscle metabolism directly have also supported the fact that there is no change in fat or carbohydrate metabolism, but these usually have had a small sample size. We combined the data from muscle biopsy analyses of several similar studies to generate a sample size of 16-44, depending on the measure. We examined muscle glycogen, citrate, acetyl-CoA, glucose-6-phosphate, and cyclic adenosine monophosphate (cAMP) in resting samples and in those obtained after 10-15 min of exercise at 70%-85% maximal oxygen consumption. Exercise decreased (p < 0.05) glycogen and increased (p < 0.05) citrate, acetyl-CoA, and glucose-6-phosphate. The only effects of caffeine were to increase (p < 0.05) citrate in resting muscle and cAMP in exercise. There is very little evidence to support the hypothesis that caffeine has ergogenic effects as a result of enhanced fat oxidation. Individuals may, however, respond differently to the effects of caffeine, and there is growing evidence that this could be explained by common genetic variations.

Rapid exercise-induced changes in PGC-1alpha mRNA and protein in human skeletal muscle.

The mRNA of the nuclear coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) increases during prolonged exercise and is influenced by carbohydrate availability. It is unknown if the increases in mRNA reflect the PGC-1alpha protein or if glycogen stores are an important regulator. Seven male subjects [23 +/- 1.3 yr old, maximum oxygen uptake (Vo(2 max)) 48.4 +/- 0.8 ml.kg(-1).min(-1)] exercised to exhaustion ( approximately 2 h) at 65% Vo(2 max) followed by ingestion of either a high-carbohydrate (HC) or low-carbohydrate (LC) diet (7 or 2.9 g.kg(-1).day(-1), respectively) for 52 h of recovery. Glycogen remained depressed in LC (P < 0.05) while returning to resting levels by 24 h in HC. PGC-1alpha mRNA increased both at exhaustion (3-fold) and 2 h later (6.2-fold) (P < 0.05) but returned to rest levels by 24 h. PGC-1alpha protein increased (P < 0.05) 23% at exhaustion and remained elevated for at least 24 h (P < 0.05). While there was no direct treatment effect (HC vs. LC) for PGC-1alpha mRNA or protein, there was a linear relationship between the changes in glycogen and those in PGC-1alpha protein during exercise and recovery (r = -0.68, P < 0.05). In contrast, PGC-1beta did not increase with exercise but rather decreased (P < 0.05) below rest level at 24 and 52 h, and the decrease was greater (P < 0.05) in LC. PGC-1alpha protein content increased in prolonged exercise and remained upregulated for 24 h, but this could not have been predicted by the changes in mRNA. The beta-isoform declined rather than increasing, and this was greater when glycogen was not resynthesized to rest levels.