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Effects of chronic decaffeinated green tea extract supplementation on lipolysis and substrate utilization during upper body exercise.
Blicher, S, Bartholomae, E, Kressler, J
Journal of sport and health science. 2021;(2):237-242
Abstract
BACKGROUND Decaffeinated green tea extract (dGTE) can increase fat oxidation during leg exercise, but dGTE is unsuitable for many people (e.g., those with injuries/disabilities), and its effects on arm exercise and women are unknown. METHODS Eight adults (23-37 years old, 4 women) performed an incremental arm cycle test to measure peak oxygen uptake (VO2peak), followed by four 1-h trials at 50% VO2peak. Subjects were randomly assigned to 650 mg of dGTE or placebo (PLA) for 4 weeks followed by a 4-week washout and crossover trial. Blood samples were obtained pre-exercise and post-exercise for glycerol and free fatty acid analysis. Respiratory gases were collected continuously. RESULTS VO2 showed no differences across trials ((0.83-0.89) ± (0.19-0.25) L/min, p = 0.460), neither did energy expenditure ((264-266) ± (59-77) kcal, p = 0.420) nor fat oxidation (dGTE = 0.11 to 0.12 g/min vs. PLA = 0.10 to 0.09 g/min, p = 0.220). Fat oxidation as percentage of energy expenditure was not different for dGTE vs. PLA (23% ± 12% to 25% ± 11% vs. 23% ± 10% to 21% ± 9%, p = 0.532). Glycerol concentration increased post-exercise in all trials, independent of treatments (pre = (3.4-5.1) ± (0.6-2.6) mg/dL vs. post = (7.9-9.8) ± (2.6-3.7) mg/dL, p = 0.867, η2 = 0.005 for interaction), as did free fatty acid ((3.5-4.8) ± (1.4-2.2) mg/dL vs. (7.2-9.1) ± (2.6-4.5) mg/dL, p = 0.981, η2 = 0.000). CONCLUSION Chronic dGTE supplementation had no effect on lipolysis and fat oxidation during arm cycle exercise in men and women.
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Liver-Oriented Acute Metabolic Effects of A Low Dose of L-Carnitine under Fat-Mobilizing Conditions: Pilot Human Clinical Trial.
Odo, S, Tanabe, K, Yohda, M, Yamauchi, M
Journal of nutritional science and vitaminology. 2020;(2):136-149
Abstract
The acute metabolic effect of low dosages of L-carnitine under fat-mobilizing conditions was investigated. Healthy subjects (Study 1: n=5; Study 2: n=6) were asked to fast overnight. Then, 30 min of aerobic exercise on a cycle ergometer was performed after supplementation, followed by a 3.5-h sedentary recovery phase. The following ingestion patterns were used: Study 1 (i) noningestion, (ii) 750 mg of L-carnitine (LC), and (iii) 750 mg of LC+50 g of carbohydrate (CHO); Study 2 (iv) noningestion, (v) 500 mg of LC, (vi) 30 mg of CoQ10, and (vii) 500 mg of LC+30 mg of CoQ10. The energy expenditure (EE) and nonprotein respiratory quotient (npRQ) were measured during the pre-exercise, postexercise, and recovery periods. Serum free carnitine, acetylcarnitine, total carnitine (Study 1 and 2), and ketone bodies (Study 2) were measured. The 750 mg LC treatment significantly facilitated fat oxidation during the recovery phases (p<0.05) without elevating EE. The higher fat oxidation associated with LC was completely suppressed by CHO. CoQ10 affected neither npRQ nor EE. npRQ was significantly correlated with the serum total ketone bodies (R=-0.68, p<0.001) and acetylcarnitine (R=-0.61--0.70, p<0.001). The highest correlation was found between acetylcarnitine and total ketone bodies immediately after exercise (R=0.85, p<0.001). In conclusion, LC enhanced liver fat utilization and ketogenesis in an acute manner without stimulating EE under fat-mobilizing conditions.
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Sex Differences in Adipose Tissue Function.
Gavin, KM, Bessesen, DH
Endocrinology and metabolism clinics of North America. 2020;(2):215-228
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Abstract
Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.
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Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans.
Laurens, C, Parmar, A, Murphy, E, Carper, D, Lair, B, Maes, P, Vion, J, Boulet, N, Fontaine, C, Marquès, M, et al
JCI insight. 2020;(6)
Abstract
We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise-stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.
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Leptin-Mediated Changes in the Human Metabolome.
Lawler, K, Huang-Doran, I, Sonoyama, T, Collet, TH, Keogh, JM, Henning, E, O'Rahilly, S, Bottolo, L, Farooqi, IS
The Journal of clinical endocrinology and metabolism. 2020;(8):2541-52
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Abstract
CONTEXT While severe obesity due to congenital leptin deficiency is rare, studies in patients before and after treatment with leptin can provide unique insights into the role that leptin plays in metabolic and endocrine function. OBJECTIVE The aim of this study was to characterize changes in peripheral metabolism in people with congenital leptin deficiency undergoing leptin replacement therapy, and to investigate the extent to which these changes are explained by reduced caloric intake. DESIGN Ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was used to measure 661 metabolites in 6 severely obese people with congenital leptin deficiency before, and within 1 month after, treatment with recombinant leptin. Data were analyzed using unsupervised and hypothesis-driven computational approaches and compared with data from a study of acute caloric restriction in healthy volunteers. RESULTS Leptin replacement was associated with class-wide increased levels of fatty acids and acylcarnitines and decreased phospholipids, consistent with enhanced lipolysis and fatty acid oxidation. Primary and secondary bile acids increased after leptin treatment. Comparable changes were observed after acute caloric restriction. Branched-chain amino acids and steroid metabolites decreased after leptin, but not after acute caloric restriction. Individuals with severe obesity due to leptin deficiency and other genetic obesity syndromes shared a metabolomic signature associated with increased BMI. CONCLUSION Leptin replacement was associated with changes in lipolysis and substrate utilization that were consistent with negative energy balance. However, leptin's effects on branched-chain amino acids and steroid metabolites were independent of reduced caloric intake and require further exploration.
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Hydrogen Sulfide in the Adipose Tissue-Physiology, Pathology and a Target for Pharmacotherapy.
Bełtowski, J, Jamroz-Wiśniewska, A
Molecules (Basel, Switzerland). 2016;(1)
Abstract
Hydrogen sulfide (H₂S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H₂S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing cyclic AMP concentration. The effect of H₂S on adipose tissue insulin sensitivity and glucose uptake is controversial. Some studies suggest that H₂S inhibits insulin-induced glucose uptake and that excess of H₂S contributes to adipose tissue insulin resistance in metabolic syndrome. In contrast, other studies have demonstrated that H₂S stimulates glucose uptake and its deficiency contributes to insulin resistance. Similarly, the effect of H₂S on adipose tissue lipolysis is controversial. H₂S produced by perivascular adipose tissue decreases vascular tone by activating ATP-sensitive and/or voltage-gated potassium channels in smooth muscle cells. Experimental obesity induced by high calorie diet has a time dependent effect on H₂S in perivascular adipose tissue; short and long-term obesity increase and decrease H₂S production, respectively. Hyperglycemia has been consistently demonstrated to suppress CSE-H₂S pathway in various adipose tissue depots. Finally, H₂S deficiency may contribute to adipose tissue inflammation associated with obesity/metabolic syndrome.
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Effects of Genetic Loci Associated with Central Obesity on Adipocyte Lipolysis.
Strawbridge, RJ, Laumen, H, Hamsten, A, Breier, M, Grallert, H, Hauner, H, Arner, P, Dahlman, I
PloS one. 2016;(4):e0153990
Abstract
OBJECTIVES Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. SUBJECTS AND METHODS Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7-62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. RESULTS The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. SIGNIFICANCE This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes.
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Adipose Tissue Free Fatty Acid Storage In Vivo: Effects of Insulin Versus Niacin as a Control for Suppression of Lipolysis.
Ali, AH, Mundi, M, Koutsari, C, Bernlohr, DA, Jensen, MD
Diabetes. 2015;(8):2828-35
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Insulin stimulates the translocation fatty acid transport protein 1 (FATP1) to plasma membrane, and thus greater free fatty acid (FFA) uptake, in adipocyte cell models. Whether insulin stimulates greater FFA clearance into adipose tissue in vivo is unknown. We tested this hypothesis by comparing direct FFA storage in subcutaneous adipose tissue during insulin versus niacin-medicated suppression of lipolysis. We measured direct FFA storage in abdominal and femoral subcutaneous fat in 10 and 11 adults, respectively, during euglycemic hyperinsulinemia or after oral niacin to suppress FFA compared with 11 saline control experiments. Direct palmitate storage was assessed using a [U-(13)C]palmitate infusion to measure palmitate kinetics and an intravenous palmitate radiotracer bolus/timed biopsy. Plasma palmitate concentrations and flux were suppressed to 23 ± 3 and 26 ± 5 µmol ⋅ L(-1) (P = 0.91) and 44 ± 4 and 39 ± 5 µmol ⋅ min(-1) (P = 0.41) in the insulin and niacin groups, respectively, much less (P < 0.001) than the saline control group (102 ± 8 and 104 ± 12 µmol ⋅ min(-1), respectively). In the insulin, niacin, and saline groups, abdominal palmitate storage rates were 0.25 ± 0.05 vs. 0.25 ± 0.07 vs. 0.32 ± 0.05 µmol ⋅ kg adipose lipid(-1) ⋅ min(-1), respectively (P = NS), and femoral adipose storage rates were 0.19 ± 0.06 vs. 0.20 ± 0.05 vs. 0.31 ± 0.05 µmol ⋅ kg adipose lipid(-1) ⋅ min(-1), respectively (P = NS). In conclusion, insulin does not increase FFA storage in adipose tissue compared with niacin, which suppresses lipolysis via a different pathway.
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A review of the receptor binding and pharmacological effects of N-methyltyramine.
Stohs, SJ, Hartman, MJ
Phytotherapy research : PTR. 2015;(1):14-6
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Abstract
N-methyltyramine (NMT) is a protoalkaloid isolated from various plant species. It is assumed that NMT is an adrenergic agonist with pharmacological properties similar to other structurally related biogenic amines. Current research studies indicate that NMT is an α-adrenoreceptor antagonist, and exhibits modest inhibitory (antagonistic) activity with respect to the breakdown of fats (lipolysis). Furthermore, NMT has been shown to enhance appetite and digestion of foods through its stimulatory effects on gastrin and pancreatic secretions. As a consequence, NMT is not an ingredient that should be used in dietary supplements designed to promote weight loss. It may result in an increase in perceived energy by promoting appetite and the digestion and absorption of nutrients while inhibiting the breakdown to fats to energy.
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Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects.
Lee, SR, Schriefer, JM, Gunnels, TA, Harvey, IC, Bloomer, RJ
Lipids in health and disease. 2013;:148
Abstract
BACKGROUND Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. METHODS Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6-8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. RESULTS A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. CONCLUSION Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.