Increased Fat Oxidation Research Articles

204-OR: Inhibition of Hepatic ACC on a High-Fat Diet Results in Hyperglycemia and Hepatomegaly Due to Excess Energy Generation

Liver triglyceride accumulation associated with insulin resistance is partially mediated by elevated de novo lipogenesis (DNL); thus, limiting this pathway is a promising therapeutic strategy for NAFLD. Targeted suppression of acetyl-CoA carboxylase (ACC) activity depletes malonyl-CoA resulting in lower DNL and a simultaneous increase in fat oxidation due to activation of CPT-1. Recently developed ACC1/2 liver specific double KO mice (LDKO) are protected from hepatic steatosis and closely recapitulate pharmacological inhibition of ACC1/2 in humans with NAFLD. However, hepatic ACC inhibition causes surprising elevations in circulating triglyceride and glucose concentrations. LDKO mice had worsened glucose tolerance, which was most consequential during a HFD and especially prominent during fasting. Glucose labeling from 2H2O and [U-13C3] lactate was higher in LDKO hepatocytes, an effect that was dependent on the availability of long chain fatty acids, suggesting that loss of malonyl-CoA and activation of CPT-1 promote gluconeogenesis (GNG). Ketogenesis was increased in LDKO hepatocytes and showed limited response to insulin. Acetyl-CoA was elevated in the fed state, as previously reported, but was normal during fasting when hyperglycemia was most prominent. LDKO mice exhibited massive accumulation of liver citrate and a high fasted hepatic energy charge, which are both known to activate GNG. Hence, despite improved hepatic lipid profile and insulin sensitivity, LDKO liver activates GNG. The resulting hyperinsulinemia partially ameliorates the glycemia phenotype, but may also induce hepatomegaly through canonical signaling pathways and effects on energy status. Thus, activation of fat oxidation in liver lowers lipid accumulation, but has downstream metabolic effects on energetically dependent pathways, such as GNG, that may promote elevated glucose levels in contexts of reduced insulin action, such as fasting and diet induced obesity. Disclosure S. Deja: None. J.A. Fletcher: None. B. Kucejova: None. X. Fu: None. C. Kim: None. J. Browning: None. J.D. Horton: Board Member; Self; Pfizer Inc. Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Catabasis Pharmaceuticals. Other Relationship; Self; Regeneron Pharmaceuticals, Sanofi. S.C. Burgess: None. Funding National Institutes of Health (R01DK078184, P41EB015908); Robert A. Welch Foundation (I-1804)

Low-intensity exercise stimulates bioenergetics and increases fat oxidation in mitochondria of blood mononuclear cells from sedentary adults.

AimExercise training induces adaptations in muscle and other tissue mitochondrial metabolism, dynamics, and oxidative phosphorylation capacity. Mitochondrial fatty acid oxidation was shown to be pivotal for the anti‐inflammatory status of immune cells. We hypothesize that exercise training can exert effects influence mitochondrial fatty acid metabolism in peripheral blood mononuclear cells (PBMCs). The aim was to investigate the effect of exercise on the fatty acid oxidation‐dependent respiration in PBMCs.DesignTwelve fasted or fed volunteers first performed incremental‐load exercise tests to exhaustion on a cycle ergometer to determine the optimal workload ensuring maximal health benefits in volunteers with a sedentary lifestyle. In addition, the same volunteers performed 60 min of low‐intensity constant‐load exercise.ResultsIn the incremental‐load exercise, the maximal whole‐body fat oxidation rate measured by indirect calorimetry was reached at the fasted state already at a 50 W workload. At the 75–175 W workloads, the contribution of fat oxidation significantly decreased to only 11%, the heart rate increased to 185 BPM, and the study participants reached exhaustion. These results show that low‐intensity exercise (50W) is optimal for maximal whole‐body fat utilization. After low‐intensity exercise, the ROUTINE mitochondrial respiration, as well as fatty acid oxidation‐dependent respiration in PBMCs at LEAK and OXPHOS states, were significantly increased by 31%, 65%, and 76%, respectively. In addition, during 60 min of low‐intensity (50W) exercise, a 2‐fold higher lipolysis rate was observed and 13.5 ± 0.9 g of fat was metabolized, which was 57% more than the amount of fat that was metabolized during the incremental‐load exercise.ConclusionsIn individuals with a sedentary lifestyle participating in a bicycle ergometry exercise program, maximal lipolysis and whole‐body fat oxidation rate is reached in a fasted state during low‐intensity exercise. For the first time, it was demonstrated that low‐intensity exercise improves bioenergetics and increases fatty acid oxidation in PBMCs and may contribute to the anti‐inflammatory phenotype.

SAT-LB8 The Testosterone-To-Estradiol Ratio, Rather Than Testosterone or Estradiol Alone, Is a More Precise Marker of Metabolic-Related Outcomes in Males: Insights From a Systematic Review

Background:Estradiol (E2) has been shown to exert beneficial effects on males, particularly for metabolic outcomes. However, these benefits tend to be more evident when accompanied by concurrent increase in testosterone (T) levels, when the increase of E2 is secondary to the increase of T. Oppositely to its benefits in healthy males, when under metabolic and inflammatory diseases, E2 has been reported to be a marker of worse prognosis, once E2 is unproportionally high compared to testosterone in pathological conditions, which results in hypogonadism. The collective analysis of T and E2 shows that the balance between these two hormones determines whether increase in E2 levels is physiological or pathological, demonstrated by balanced T and E2, i.e., intact T:E2 ratio compared to healthy males, and disrupted balance between T and E2, with impaired T:E2 ratio, respectivey. Hence, it seems that the dual relationship between E2 and health markers in males is based on the balance, or ratio, between T and E2. The objective of the present study is to propose a ratio between T and E2(testosterone-to-estradiol ratio, or T:E ratio) as a better predictor of health outcomes than testosterone or estradiol alone, and to differentiate health from pathological states within this single marker, from a review of the literature. Methods:We systematically searched for articles using the following criteria: 1. Any of the combinations of the expressions “testosterone” (AND) ”estradiol” (AND) “male(s)” (OR) ”men” (OR) “masculine”, or “testosterone-to-estradiol” (OR) “testosterone:estradiol” (OR) “estradiol-to-testosterone ratio” (OR) “estradiol:testosterone” (AND) “male(s)” (OR) ”men” (OR) “masculine”, to be present in the title and/or abstract; 2. Fully written in English; 3. Performed in humans; 4. Throughout the literature until Jan 30th 202020; and 5. Original researches.Results:We selected 39 articles, from which 27 were performed in healthy males, and 11 under metabolic or inflammatory conditions. Benefits of E2 in healthy males occurred irrespective of T for bone mass and quality, and anger levels. Benefits that were better identified when E2 and T were evaluated together include better libido, improved cognitive functions, improved well-being and other mood states, increased muscle mass, enhanced loss of fat mass, quality, increased basal metabolic rate, increased fat oxidation, and reduced cardiovascular markers, including reduced maximal intimal-media carotids thickness, when T:E ratio was > 13.7. In pathological states, increased estradiol was associated to increased risk of disease-specific complications, and worse quality of life, particularly when T:E was < 9.5. T:E ratio was also able to accurately identify healthy athletes from those affected by any sport-related metabolic conditions.Conclusion:Testosterone-to-estradiol (T:E) ratio is likely a more precise predictor of metabolic-related health outcomes in both healthy and pathological states, compared to testosterone or estradiol alone.

Hourly 4-s Sprints Prevent Impairment of Postprandial Fat Metabolism from Inactivity.

This study determined if the interruption of prolonged sitting (i.e., 8 h of inactivity) with hourly cycling sprints of only 4-s duration each (i.e., 4 s × 5 per hour × 8 h = 160 s·d SPRINTS) improves PPL. The 4-s sprints used an inertial load ergometer and were followed by 45 s of seated rest. Four men and four women participated in two trials. Interventions consisted of an 8-h period of sitting (SIT), or a trial with equal sitting time interrupted with five SPRINTS every hour. The morning after the interventions, PPL and fat oxidation were measured over a 6-h period. Plasma glucose, insulin, and triglyceride concentrations were measured bihourly and incremental area under the curve (AUC) was calculated. No differences (P > 0.05) between interventions were found for plasma insulin or glucose AUC. However, SPRINTS displayed a 31% (408 ± 119 vs 593 ± 88 mg·dL per 6 h; P = 0.009) decrease in plasma triglyceride incremental AUC and a 43% increase in whole-body fat oxidation (P = 0.001) when compared with SIT. These data indicate that hourly very short bouts (4 s) of maximal intensity cycle sprints interrupting prolonged sitting can significantly lower the next day's postprandial plasma triglyceride response and increase fat oxidation after a high-fat meal in healthy young adults. Given that these improvements were elicited from only 160 s of nonfatiguing exercise per day, it raises the question as to what is the least amount of exercise that can acutely improve fat metabolism and other aspects of health.

Reducing endogenous insulin is linked with protection against hepatic steatosis in mice

BackgroundObesity and type 2 diabetes (T2D) are closely associated with hepatic steatosis (HS), which if untreated can advance to serious liver conditions. Since insulin promotes hepatic lipogenesis, reducing hyperinsulinemia may help in treating HS. E4orf1 is an adenovirus-derived protein that improves glucose clearance independent of insulin, lowers insulin amount required for glucose disposal, and reduces HS. As a next step, we evaluated the mechanism for E4orf1-induced reduction in HS and tested that E4orf1 does not induce hypoglycemia, an important attribute for its application as a potential anti-diabetic agent.MethodsC57Bl/6J mice that transgenically express E4orf1 in adipose tissue (E4orf-Tg) and wild-type (WT) mice received a chow diet for 6 weeks, followed by a high-fat (HF) diet for additional 10 weeks. Body composition, blood glucose, and serum insulin levels upon glucose load were measured at 0, 6, 7, and 16 weeks. Serum free fatty acid (FFA), triglyceride (TG), and hepatic TG were measured at study termination. We compared histology and the mRNA/protein markers of hepatic and adipose tissue lipid metabolism between the two groups of mice.ResultsOn chow diet, both groups remained normoglycemic, but E4orf1 expression reduced insulin response. On HF diet, glycemic control in WT deteriorated, whereas E4orf1 significantly enhanced glycemic control, lowered insulin response, reduced hepatic triglycerides, and serum FFA. Overall, a comparison of hepatic mRNA and/or protein expression suggested that E4orf1 expression significantly decreased de novo lipogenesis (DNL) and intracellular lipid transport and increased fat oxidation and TG export. Adipose tissue mRNA and protein markers suggested that E4orf1 expression lowered DNL and increased lipolysis.ConclusionConsidering that E4orf1 is not secreted in circulation, we postulate that reduced endogenous insulin in E4orf1 mice indirectly contributes to reduce HS by altering hepatic lipid metabolism, including lipogenesis. This study underscores the possibility of indirectly impacting HS by manipulating adipose tissue metabolism.

Maximum Aerobic Function: Clinical Relevance, Physiological Underpinnings, and Practical Application.

The earliest humans relied on large quantities of metabolic energy from the oxidation of fatty acids to develop larger brains and bodies, prevent and reduce disease risk, extend longevity, in addition to other benefits. This was enabled through the consumption of a high fat and low-carbohydrate diet (LCD). Increased fat oxidation also supported daily bouts of prolonged, low-intensity, aerobic-based physical activity. Over the past 40-plus years, a clinical program has been developed to help people manage their lifestyles to promote increased fat oxidation as a means to improve various aspects of health and fitness that include reducing excess body fat, preventing disease, and optimizing human performance. This program is referred to as maximum aerobic function, and includes the practical application of a personalized exercise heart rate (HR) formula of low-to-moderate intensity associated with maximal fat oxidation (MFO), and without the need for laboratory evaluations. The relationship between exercise training at this HR and associated laboratory measures of MFO, health outcomes and athletic performance must be verified scientifically.

The Effects of Low- and High-Glycemic Index Sport Nutrition Bars on Metabolism and Performance in Recreational Soccer Players.

Consumption of low-glycemic index (GI) carbohydrates (CHO) may be superior to high-GI CHO before exercise by increasing fat oxidation and decreasing carbohydrate oxidation. We compared the effects of pre-exercise feeding of a low-GI lentil-based sports nutrition bar with a high-GI bar on metabolism and performance during a simulated soccer match. Using a randomized, double-blind, counterbalanced, crossover design, participants (n = 8) consumed 1.5 g/kg available CHO from a low-GI bar (GI = 45) or high-GI bar (GI = 101) two hours before a 90 min simulated soccer match, and 0.38 g/kg body mass during a 15 min half-time break. The test involved alternating 6 min intervals of paced jogging, running, walking, and sprinting, and 3 min intervals of soccer-specific skills (timed ball dribbling, agility running, heading, kicking accuracy). Carbohydrate oxidation rate was lower during the match after consuming the low-GI compared to high-GI bar (2.17 ± 0.6 vs. 2.72 ± 0.4 g/min; p < 0.05). Participants performed better during the low-GI versus high-GI bar condition on the agility test (5.7 ± 0.4 versus 6.1 ± 0.6 s; p < 0.01) and heading (i.e., jumping height 24.7 ± 4.3 versus 22.2 ± 4.5 cm; p < 0.01) late in the soccer match (72 min). A low-GI lentil-based sports nutrition bar provides a metabolic benefit (lower carbohydrate oxidation rate) and a modest improvement in agility running and jumping height (heading) late in the test.

Exogenous lactate increases fat oxidation in resting rats

BackgroundLactate had been traditionally considered a fatigue‐associated byproduct of high intensity exercise. Although several physiological roles of lactate have been revealed in the last decades, its effects on energy metabolism and substrate oxidation remain unknown. Therefore, here, we investigated the effects of lactate on the energy metabolism of resting rats.MethodsMale rats were divided into control (Con; distilled water), caffeine (Caf; 10 mg/kg), lactate (Lac; 4 g/kg), and caffeine plus lactate (Caf+Lac; 10 mg + 4 g/kg) groups. After oral administration of treatments, animals were evaluated for resting energy expenditure, biochemical blood parameters, and mRNA levels of key genes involved in energy metabolism in the soleus muscle.ResultsGroups did not differ in total energy expenditure throughout the 6‐h post‐treatment evaluation. Within the first 4 h, the Lac and Caf+Lac groups showed higher fat oxidation rates than that of the Con group. Carbohydrate oxidation rates were similar between Lac and Con groups. Lactate treatment decreased blood free fatty‐acid levels and increased the mRNA expression of fatty acid translocase (FAT/CD36) and peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) in skeletal muscle.ConclusionsOur findings indicate that lactate treatment can enhance fat metabolism in whole body and skeletal muscle.Support or Funding InformationThis paper was supported by the KU Research Professor Program of Konkuk University.

Elucidation of the roles of brown and brite fat genes: GPR120 is a modulator of brown adipose tissue function.

New Findings What is the topic of this review? Activation of brown adipose tissue with G protein‐coupled receptors as key druggable targets as a strategy to increase energy consumption and reduce fat mass. What advances does it highlight? GPR120 is a fatty acid receptor highly expressed in brown adipose tissue. Its activation by selective ligands increases brown adipose tissue activity. This is mediated by changes in mitochondrial dynamics resulting in increased O2 consumption leading to enhanced nutrient uptake and a reduction in fat mass. The identification of druggable targets to stimulate brown adipose tissue (BAT) is a strategy to combat obesity due to this highly metabolically active tissue utilising thermogenesis to burn fat. Upon cold exposure BAT is activated by the sympathetic nervous system via β3‐adrenergic receptors. Determination of additional receptors expressed by brown, white and brite (brown‐in‐white) fat can lead to new pharmacological treatments to activate BAT. GPR120 is a G protein‐coupled fatty acid receptor that is highly expressed in BAT and further increases in response to cold. Activation of this receptor with the selective agonist TUG‐891 acutely increases fat oxidation and reduces fat mass in mice. The effects are coincident with increased BAT activity and enhanced nutrient uptake. TUG‐891 stimulation of brown adipocytes induces intracellular Ca2+ release which results in elevated O2 consumption as well as mitochondrial depolarisation and fission. Thus, activation of GPR120 in BAT with ligands such as TUG‐891 is a promising strategy to increase fat consumption.

Adrenergic receptors and cardiovascular effects of catecholamines

Activation of the sympathetic nervous system is responsible for the body's “fight or flight” reaction. The physiological responses to the activation of the sympathetic nervous system and adrenal medulla are mediated through the action of the endogenous catecholamines norepinephrine (or noradrenaline) and epinephrine (or adrenaline) on adrenergic receptors. Adrenergic receptors belong to the superfamily of G protein-coupled receptors (GPCR). Adrenoceptors are divided into alpha1, alpha2, beta1, beta2 and beta3 receptors. Norepinephrine stimulates both subtypes of α receptors and β1 receptors. Epinephrine stimulates all subtypes ofα and β adrenoreceptors. α1 adrenergic receptors, coupled to stimulatory Gq proteins, activate the enzyme phospholipase C and are mainly found in the smooth muscle cells of blood vessels and urinary tract, where they induce constriction. α2 receptors are coupled to inhibitory Gi proteins, that inactivate adenylyl cyclase, decreasing cyclic adenosine monophosphate (AMP) production. They are mainly found in the central nervous system, where their activation results in a decreased arterial blood pressure. β1 adrenoreceptors predominate in the heart, activate the Gs-adenylyl cyclase -cAMP-protein kinase A signaling cascade, and induce positive inotropic and chronotropic effects. β2 adrenoreceptors are distributed extensively throughout the body, but are expressed predominantly in bronchial smooth muscle cells. β2 adrenergic receptors activate adenylyl cyclase, dilate blood vessels and bronchioles, relax the muscles of the uterus, bladder and gastrointestinal duct, and also decrease platelet aggregation and glycogenolysis. β3 receptors can couple interchangeably to both stimulating and inhibiting G proteins. They are abundantly expressed in white and brown adipose tissue, and increase fat oxidation, energy expenditure and insulin-mediated glucose uptake. This review details the regulation of cardiac and vascular function by adrenergic receptors.

Dietary supplementation with New Zealand blackcurrant extract enhances fat oxidation during submaximal exercise in the heat

ObjectivesThis study investigated the effect of 7 days’ supplementation with New Zealand blackcurrant extract on thermoregulation and substrate metabolism during running in the heat. DesignRandomized, double-blind, cross-over study. MethodsTwelve men and six women (mean±SD: Age 27±6 years, height 1.76±0.10m, mass 74±12kg, V̇O2max 53.4±7.0mLkg−1min−1) completed one assessment of maximal aerobic capacity and one familiarisation trial (18°C, 40% relative humidity, RH), before ingesting 2×300mgday−1 capsules of CurraNZ™ (each containing 105mg anthocyanin) or a visually matched placebo (2×300mg microcrystalline cellulose M102) for 7 days (washout 14 days). On day 7 of each supplementation period, participants completed 60min of fasted running at 65% V̇O2max in hot ambient conditions (34°C and 40% relative humidity). ResultsCarbohydrate oxidation was decreased in the NZBC trial [by 0.24gmin−1 (95% CI: 0.21–0.27gmin-1)] compared to placebo (p= 0.014, d=0.46), and fat oxidation was increased in the NZBC trial [by 0.12gmin−1 (95% CI: 0.10 to 0.15gmin−1)], compared to placebo (p=0.008, d=0.57). NZBC did not influence heart rate (p=0.963), rectal temperature (p=0.380), skin temperature (p=0.955), body temperature (p=0.214) or physiological strain index (p=0.705) during exercise. ConclusionsSeven-days intake of 600mg NZBC extract increased fat oxidation without influencing cardiorespiratory or thermoregulatory variables during prolonged moderate intensity running in hot conditions.

The effect of using supplementing on some physiological variables and slowing the appearance of fatigue in volleyball players

Athletes are continuously searching for means to raise their performance level to the extent that exceeds their individual capabilities to achieve sportive achievements and reach advanced positions and at all levels, as increasing training loads and its dosages no longer fulfill the aspirations of athletes ;one of the most important nutritional supplements that have major impact on building the body and providing the necessary needs in rationing its construction is the Arginine compound , which is an amino acid that helps the body in building protein. Arginine has emerged in recent years as a nutritional supplement that enhances energy sources and increases the athlete's ability to endure performance. It directly affects the central nervous system (CNS) and various metabolic processes and the general result is to maintain glycogen due to increasing fat oxidation and reducing carbohydrate oxidation. The study aims to identify the effect of using a nutritional supplement on some physiological variables and to slow the appearance of fatigue for volleyball l players.

High-Fat Diet Increases Fat Oxidation and Promotes Skeletal Muscle Fatty Acid Transporter Expression in Exercise-Trained Mice.

The aim of this study was to investigate the effect of a high-fat diet (HFD) on energy substrate utilization during long-term endurance exercise in mice. Male ICR mice (n = 32; 6 weeks old) were divided into two groups: low-fat diet (LFD, n = 16) and HFD (n = 16) and acclimatized to LFD or HFD feeding over 12 weeks. After 12 weeks, the two dietary groups were each divided into two groups with or without exercise (EX): LF-CON, LF-EX, HF-CON, and HF-EX groups. The exercise groups were trained to run on a treadmill for 12 weeks. At the end of the experimental protocol, energy metabolism in the whole body was measured at rest for 24 h and during exercise for 1 h using respiratory gas analysis. Furthermore, molecules involved in skeletal muscle fat metabolism were analyzed. Substrate utilization for energy metabolism in the whole body indicated that fat utilization was high in HFD intake. Notably, when HFD intake and exercise were combined, fat utilization was markedly increased during endurance exercise. In contrast, exercise showed no effect when combined with LFD intake. The gene expressions of Fat/Cd36, Fatp1, Fabp-pm, and Cpt1 were upregulated by HFD intake, with Fat/Cd36 and Cpt1 considerably elevated during long-term endurance exercise. In contrast, exercise showed no effect when combined with LFD intake. These results suggest that HFD intake effectively increased fat utilization as an energy substrate during long-term endurance exercise.

Effect of Almond Supplementation on Non-Esterified Fatty Acid Values and Exercise Performance.

Several studies have investigated the effects of fat intake before exercise on subsequent substrate oxidation and exercise performance. While some studies have reported that unsaturated fatty acid supplementation slightly increases fat oxidation, the changes have not been reflected in the maximum oxygen uptake or in other performance and physiological parameters. We selected almonds as a fatty acid (FA) source for acute supplementation and investigated their effect on non-esterified fatty acid (NEFA) values and exercise performance. Five physically active male subjects (age 32.9 ± 12.7 years, height 178.5 ± 3.3 cm, and weight 81.3 ± 9.7 kg) were randomly assigned to take an almond or placebo supplement 2 h before participating in two cycling resistance training sessions separated by an interval of 7–10 days. Their performance was evaluated with a maximal incremental test until exhaustion. Blood samples collected before, during, and after testing were biochemically analysed. The results indicated a NEFA value average increase of 0.09 mg·dL−1 (95% CI: 0.05–0.14; p < 0.001) after active supplement intake and enhanced performance (5389 ± 1795 W vs. placebo 4470 ± 2053 W, p = 0.043) after almond supplementation compared to the placebo. The almond supplementation did not cause gastrointestinal disturbances. Our study suggests that acute almond supplementation 2 h before exercise can improve performance in endurance exercise in trained subjects.

Menstrual cycle phase does not affect whole body peak fat oxidation rate during a graded exercise test.

Female sex hormones fluctuate in a predictable manner throughout the menstrual cycle in eumenorrheic women. In studies conducted in both animal and humans, estrogen and progesterone have been found to exert individual metabolic effects during both rest and exercise, suggesting that estrogen may cause an increase in fat oxidation during exercise. However, not all studies find these metabolic changes with the natural physiological variation in the sex hormones. To date, no studies have investigated whether whole body peak fat oxidation rate (PFO) and maximal fat oxidation intensity (FATmax) are affected at different time points [mid-follicular (MF), late-follicular (LF), and mid-luteal (ML)] in the menstrual cycle, where plasma estrogen and progesterone are either at their minimum or maximum. We hypothesized that an increased plasma estrogen concentration together with low progesterone concentration in LF would result in a modest but significant increase in PFO. We found no differences in body weight, body composition, or peak oxygen uptake (V̇o2peak) between any of the menstrual phases in the 19 healthy, young eumenorrheic women included in this study. PFO [MF: 0.379 (0.324-0.433) g/min; LF: 0.375 (0.329-0.421) g/min; ML: 0.382 (0.337-0.442) g/min; mean ± (95% CI)] and resting plasma free fatty acid concentrations [MF: 392 (293-492) µmol/l; LF: 477 (324-631) µmol/l; ML: 396 (285-508) µmol/L] were also similar across the menstrual cycle phases. Contrary to our hypothesis, we conclude that the naturally occurring fluctuations in the sex hormones estrogen and progesterone do not affect the whole body PFO and FATmax in young eumenorrheic women measured during a graded exercise test.NEW & NOTEWORTHY Menstrual cycle phase does not affect the peak fat oxidation rate during a graded exercise test. Natural physiological fluctuations in estrogen do not increase peak fat oxidation rate. FATmax is not influenced by menstrual cycle phase in healthy, young eumenorrheic women.

It's well and truly time to stop stating that AMPK regulates glucose uptake and fat oxidation during exercise.

None for Perspective.

Exercise Training and Fasting: Current Insights.

Fasting is defined as the abstinence from consuming food and/or beverages for different periods of time. Both traditional and modern healthcare systems recommend fasting as a therapeutic intervention for the management of several chronic, non-infectious diseases. Exercising during a fasting state increases lipolysis in adipose tissue while also stimulating peripheral fat oxidation, resulting in increased fat utilization and weight loss. A key focus of this review is to assess whether endurance training performed while fasting induces specific training adaptations, where increased fat oxidation improves long-term endurance levels. Fasting decreases body weight, lean body and fat content in both trained and untrained individuals. Several studies indicate a broader impact of fasting on metabolism, with effects on protein and glucose metabolism in sedentary and untrained subjects. However, there are conflicting data regarding the effects of fasting on glucose metabolism in highly trained athletes. The effects of fasting on physical performance indicators also remain unclear, with some reporting a decreased performance, while others found no significant effects. Differences in experimental design, severity of calorie restriction, duration, and participant characteristics could, at least in part, explain such discordant findings. Our review of the literature suggests that there is little evidence to support the notion of endurance training and fasting-mediated increases in fat oxidation, and we recommend that endurance athletes should avoid high intensity training while fasting.

PSVII-19 Transcriptomic analysis of the liver of laying hens fed diets containing supplemental fat at early laying stages

Abstract Feeding diets containing supplemental fat to laying hens is reported to ameliorate pathogenesis of fatty liver hemorrhagic syndrome (FLHS). However, molecular mechanisms for this positive effect have not been investigated. Thus, we conducted a transcriptomic analysis of the liver of laying hens fed diets containing supplemental fat at early laying stages. Two dietary treatments included basal diets with no supplemental fat and basal diets supplemented with 3.0% tallow. A total of 256 18-week-old Hy-line Brown laying hens were allotted to 1 of 2 treatments. Diets were fed to hens for 12 weeks. At the end of the experiment (30 weeks of age), 5 hens with similar BW per treatment were euthanized to collect liver tissues. The cDNA libraries were constructed with extracted RNA from the liver tissues, and sequenced using the Illumina Nextseq 500 sequencer. Genes with False Discovery Rate (FDR) &amp;lt; 0.05 were defined as differentially expressed genes (DEGs). Results indicated that a total of 951 DEGs were identified, with 483 being up-regulated and 468 being down-regulated in the liver of hens fed diets containing 3.0% tallow. The KEGG analysis revealed that the DEGs belong to several biological pathways such as cellular signaling pathways, carbon metabolism, glycolysis, gluconeogenesis, TCA cycle, amino acid metabolism, drug metabolism, and glycerophospholipid metabolism. Especially for fatty acid metabolism, the DEGs associated with fatty acid degradation (ECI2, ACSL1, HADHA, EHHADH, ACOX1, CPT1) were up-regulated, whereas those related to fatty acid synthesis (ACACA, ACSL5, FASN) were down-regulated in the liver of hens fed diets containing 3.0% tallow, which indicates that supplemental fat in diets may increase fat oxidation but decrease fat synthesis in the liver. These results provide the molecular insights for hepatic lipid metabolisms by feeding diets containing supplemental fat to laying hens at early laying stages.

Fat-lowering effects of isorhamnetin are via NHR-49-dependent pathway in Caenorhabditis elegans

Isorhamnetin (3-O-methylquercetin), a flavonol found in dill weed, sea buckthorn berries, kale and onions, has been suggested to have anti-obesity effects, but there is limited evidence of its mechanisms of action on lipid metabolism. The goal of this study was to investigate the effects of isorhamnetin on lipid metabolism using Caenorhabditis elegans as an animal model. Isorhamnetin reduced fat accumulation without affecting food intake or energy expenditure in C. elegans. The isorhamnetin's fat-lowering effects were dependent on nhr-49, a homolog of the human peroxisome proliferator-activated receptor alpha (PPARα). Isorhamnetin upregulated an enoyl-CoA hydratase (ech-1.1, involved in fatty acid β-oxidation) and adipose triglyceride lipase (atgl-1, involved in lipolysis) via NHR-49-dependent pathway at transcriptional levels. Isorhamnetin also upregulated the C. elegans AMP-activated protein kinase (AMPK) subunits homologs (aak-1 and aak-2), involved in energy homeostasis. These results suggest that isorhamnetin reduces body fat by increasing fat oxidation in part via NHR-49/PPARα-dependent pathway.

Acute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax

p-Synephrine, the principal alkaloid of bitter orange (Citrus aurantium), is widely used in dietary supplements for weight loss due to its purported effect of increasing fat oxidation. However, there is a paucity of scientific information about its effectiveness in enhancing fat oxidation during exercise. The aim of this investigation was to determine the effect of an acute dose of p-synephrine on substrate oxidation during prolonged and constant intensity exercise. In a double-blind and randomized experiment, 14 healthy subjects performed two acute experimental trials after ingesting either p-synephrine (3mgkg-1) or a placebo (cellulose). Energy expenditure and fat oxidation rates were continuously measured by indirect calorimetry during 1h of continuous cycling at Fatmax, the intensity that induces maximal fat oxidation rate. In comparison to the placebo, energy expenditure during 1h of cycling remained unchanged with p-synephrine (698 ± 129 vs. 686 ± 123kcal, P = 0.08). However, p-synephrine increased whole-body fat oxidation (33.6 ± 10.4 vs. 37.3 ± 9.8g, P < 0.01) while also reducing carbohydrate oxidation (99.5 ± 30.4 vs. 85.0 ± 28.4g, P < 0.01). However, the magnitude of the shift on substrate oxidation induced by p-synephrine was small. Acute ingestion of p-synephrine augments fat oxidation during prolonged and constant-intensity exercise.