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Mild intermittent hypoxia exposure induces metabolic and molecular adaptations in men with obesity.
van Meijel, RLJ, Vogel, MAA, Jocken, JWE, Vliex, LMM, Smeets, JSJ, Hoebers, N, Hoeks, J, Essers, Y, Schoffelen, PFM, Sell, H, et al
Molecular metabolism. 2021;:101287
Abstract
OBJECTIVE Recent studies suggest that hypoxia exposure may improve glucose homeostasis, but well-controlled human studies are lacking. We hypothesized that mild intermittent hypoxia (MIH) exposure decreases tissue oxygen partial pressure (pO2) and induces metabolic improvements in people who are overweight/obese. METHODS In a randomized, controlled, single-blind crossover study, 12 men who were overweight/obese were exposed to MIH (15 % O2, 3 × 2 h/day) or normoxia (21 % O2) for 7 consecutive days. Adipose tissue (AT) and skeletal muscle (SM) pO2, fasting/postprandial substrate metabolism, tissue-specific insulin sensitivity, SM oxidative capacity, and AT and SM gene/protein expression were determined. Furthermore, primary human myotubes and adipocytes were exposed to oxygen levels mimicking the hypoxic and normoxic AT and SM microenvironments. RESULTS MIH decreased systemic oxygen saturation (92.0 ± 0.5 % vs 97.1 ± 0.3, p < 0.001, respectively), AT pO2 (21.0 ± 2.3 vs 36.5 ± 1.5 mmHg, p < 0.001, respectively), and SM pO2 (9.5 ± 2.2 vs 15.4 ± 2.4 mmHg, p = 0.002, respectively) compared to normoxia. In addition, MIH increased glycolytic metabolism compared to normoxia, reflected by enhanced fasting and postprandial carbohydrate oxidation (pAUC = 0.002) and elevated plasma lactate concentrations (pAUC = 0.005). Mechanistically, hypoxia exposure increased insulin-independent glucose uptake compared to standard laboratory conditions (~50 %, p < 0.001) and physiological normoxia (~25 %, p = 0.019) through AMP-activated protein kinase in primary human myotubes but not in primary human adipocytes. MIH upregulated inflammatory/metabolic pathways and downregulated extracellular matrix-related pathways in AT but did not alter systemic inflammatory markers and SM oxidative capacity. MIH exposure did not induce significant alterations in AT (p = 0.120), hepatic (p = 0.132) and SM (p = 0.722) insulin sensitivity. CONCLUSIONS Our findings demonstrate for the first time that 7-day MIH reduces AT and SM pO2, evokes a shift toward glycolytic metabolism, and induces adaptations in AT and SM but does not induce alterations in tissue-specific insulin sensitivity in men who are overweight/obese. Future studies are needed to investigate further whether oxygen signaling is a promising target to mitigate metabolic complications in obesity. CLINICAL TRIAL REGISTRATION This study is registered at the Netherlands Trial Register (NL7120/NTR7325).
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Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans.
Ravussin, E, Beyl, RA, Poggiogalle, E, Hsia, DS, Peterson, CM
Obesity (Silver Spring, Md.). 2019;(8):1244-1254
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Abstract
OBJECTIVE Eating earlier in the daytime to align with circadian rhythms in metabolism enhances weight loss. However, it is unknown whether these benefits are mediated through increased energy expenditure or decreased food intake. Therefore, this study performed the first randomized trial to determine how meal timing affects 24-hour energy metabolism when food intake and meal frequency are matched. METHODS Eleven adults with overweight practiced both early time-restricted feeding (eTRF) (eating from 8 am to 2 pm) and a control schedule (eating from 8 am to 8 pm) for 4 days each. On the fourth day, 24-hour energy expenditure and substrate oxidation were measured by whole-room indirect calorimetry, in conjunction with appetite and metabolic hormones. RESULTS eTRF did not affect 24-hour energy expenditure (Δ = 10 ± 16 kcal/d; P = 0.55). Despite the longer daily fast (intermittent fasting), eTRF decreased mean ghrelin levels by 32 ± 10 pg/mL (P = 0.006), made hunger more even-keeled (P = 0.006), and tended to increase fullness (P = 0.06-0.10) and decrease the desire to eat (P = 0.08). eTRF also increased metabolic flexibility (P = 0.0006) and decreased the 24-hour nonprotein respiratory quotient (Δ = -0.021 ± 0.010; P = 0.05). CONCLUSIONS Meal-timing interventions facilitate weight loss primarily by decreasing appetite rather than by increasing energy expenditure. eTRF may also increase fat loss by increasing fat oxidation.
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Impact to short-term high intensity intermittent training on different storages of body fat, leptin and soluble leptin receptor levels in physically active non-obese men: A pilot investigation.
Caldeira, RS, Panissa, VLG, Inoue, DS, Campos, EZ, Monteiro, PA, Giglio, BM, Pimentel, GD, Hofmann, P, Lira, FS
Clinical nutrition ESPEN. 2018;:186-192
Abstract
BACKGROUND & AIMS Studies have postulated High Intensity Intermittent Training (HIIT) as a superior strategy to reduce body fat. The purpose of this study was to compare the effects HIIT and steady-state training (SST) on body composition, leptin, soluble leptin receptor (sOB-R) levels, and hunger perception in physically active non-obese men. METHODS Twenty men performed five weeks of HIIT (5 km - 1 min running at 100% speed correspondent to VȩO2peak - v VȩO2peak - interspersed with 1-min passive recovery; n = 10) or SST (5 km at 70% of vVȩO2peak continuously; n = 10) three times a week. Body composition, and hunger perception were assessed at pre- and post-training and were compared by a two-way analysis (group and training period) with repeated measures in the second factor. A fasting time-course (baseline, 24 h, and 48 h after an experimental session of exercise) of leptin and sOB-R levels were measured at pre- and post-five weeks of training and assessed by a three-way analysis (group, period and time of measurement) with repeated measures in the second and third factors. RESULTS There was no effect on body composition and hunger perception. Leptin was reduced in both groups, while sOB-R was increased post-five weeks of training in HIIT but not in the SST. CONCLUSIONS Although both training groups exerted alterations in leptin levels, only HIIT was able increased sOB-R levels, this suggest a superior impact on central responses in physically active non-obese men.
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Dynamics of fat absorption and effect of sham feeding on postprandial lipema.
Chavez-Jauregui, RN, Mattes, RD, Parks, EJ
Gastroenterology. 2010;(5):1538-48
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BACKGROUND & AIMS Given the importance of postprandial hyperlipidemia to increase risk for atherosclerosis, in the present study, stable isotope-labeled meals were fed to healthy subjects (7 males and 3 females) to investigate the kinetics chylomicron synthesis and the effect of sensory exposure to lipid on metabolism. METHODS Subjects performed two, 24-hour inpatient studies that entailed consumption of a liquid formula evening meal containing 30 g of oil (+ (13)C(2) triolein) on day 1. Breakfast (day 2) consisted of triacylglycerols (TAGs) fed as capsules (30 g oil + (13)C(7) triolein) to avoid activation of mouth taste receptors. Next, modified sham feeding of cream cheese occurred over 2 hours. In the 2 trials, the stimulus was either higher fat (HF) or lower fat (LF) cream cheese. A liquid meal was consumed at lunch. Blood sampling occurred intermittently, and chylomicron particles S(f) >400 TAGs were analyzed by gas chromatography-mass spectrometry. RESULTS (13)C(2)-Label was found in fasting-state lipoproteins, and persons with higher body fat percentages showed greater dilution of meal TAGs from endogenous sources. For both trials, 13% ± 4% of lipoprotein TAGs oleic acid was derived from the previous evening meal. Incremental area under the curve for TAGs during HF was ∼2.5 times higher than after LF exposure (46 ± 15 vs 17 ± 5 μmol/L/h; P = .04). The greater HF morning lipemia occurred with elevated glucose, insulin, and nonesterified fatty acids peak after lunch. CONCLUSIONS These data support a connection between enteral lipid metabolism and oral fat exposure, resulting in elevated postprandial lipemia. The results suggest that the intestine may participate in a mechanism coordinating oral fat signaling with control of subsequent macronutrient disposal in the body.
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The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women.
Trapp, EG, Chisholm, DJ, Freund, J, Boutcher, SH
International journal of obesity (2005). 2008;(4):684-91
Abstract
OBJECTIVE To determine the effects of a 15-week high-intensity intermittent exercise (HIIE) program on subcutaneous and trunk fat and insulin resistance of young women. DESIGN AND PROCEDURES Subjects were randomly assigned to one of the three groups: HIIE (n=15), steady-state exercise (SSE; n=15) or control (CONT; n=15). HIIE and SSE groups underwent a 15-week exercise intervention. SUBJECTS Forty-five women with a mean BMI of 23.2+/-2.0 kg m(-2) and age of 20.2+/-2.0 years. RESULTS Both exercise groups demonstrated a significant improvement (P<0.05) in cardiovascular fitness. However, only the HIIE group had a significant reduction in total body mass (TBM), fat mass (FM), trunk fat and fasting plasma insulin levels. There was significant fat loss (P<0.05) in legs compared to arms in the HIIE group only. Lean compared to overweight women lost less fat after HIIE. Decreases in leptin concentrations were negatively correlated with increases in VO(2peak) (r=-0.57, P<0.05) and positively correlated with decreases in TBM (r=0.47; P<0.0001). There was no significant change in adiponectin levels after training. CONCLUSIONS HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat, subcutaneous leg and trunk fat, and insulin resistance in young women.