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Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.

ABSTRACT: Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity.We tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis.Preexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice.Our data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.

SUBMITTER: Chung H

PROVIDER: S-EPMC5123758 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.

Chung Heekyung H Chou Winjet W Sears Dorothy D DD Patterson Ruth E RE Webster Nicholas J G NJ Ellies Lesley G LG

Metabolism: clinical and experimental 20160922 12

<h4>Background</h4>Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, ha ...[more]

PMID: 27832862

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Project description:BACKGROUND:Altering the temporal distribution of energy intake (EI) and introducing periods of intermittent fasting (IF) exert important metabolic effects. Restricting EI to earlier in the day [early time-restricted feeding (eTRF)] is a novel type of IF. OBJECTIVES:We assessed the chronic effects of eTRF compared with an energy-matched control on whole-body and skeletal muscle insulin and anabolic sensitivity. METHODS:Sixteen healthy males (aged 23 ± 1 y; BMI 24.0 ± 0.6 kg·m-2) were assigned to 2 groups that underwent either 2 wk of eTRF (n = 8) or control/caloric restriction (CON:CR; n = 8) diet. The eTRF diet was consumed ad libitum and the intervention was conducted before the CON:CR, in which the diet was provided to match the reduction in EI and body weight observed in eTRF. During eTRF, daily EI was restricted to between 08:00 and 16:00, which prolonged the overnight fast by ?5 h. The metabolic responses to a carbohydrate/protein drink were assessed pre- and post-interventions following a 12-h overnight fast. RESULTS:When compared with CON:CR, eTRF improved whole-body insulin sensitivity [between-group difference (95% CI): 1.89 (0.18, 3.60); P = 0.03; ?2p = 0.29] and skeletal muscle uptake of glucose [between-group difference (95% CI): 4266 (261, 8270) ?mol·min-1·kg-1·180 min; P = 0.04; ?2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455) nmol·min-1·kg-1·180 min; P = 0.01; ?2p = 0.44]. eTRF caused a reduction in EI (?400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01) that was matched in CON:CR (-1.24 ± 0.35 kg; P = 0.01). CONCLUSIONS:Under free-living conditions, eTRF improves whole-body insulin sensitivity and increases skeletal muscle glucose and BCAA uptake. The metabolic benefits of eTRF are independent of its effects on weight loss and represent chronic adaptations rather than the effect of the last bout of overnight fast. This trial was registered at clinicaltrials.gov as NCT03969745.

Project description:BackgroundTime-restricted feeding is an emerging dietary intervention that is becoming increasingly popular. There are, however, no randomised clinical trials of time-restricted feeding in overweight patients with type 2 diabetes. Here, we explored the effects of time-restricted feeding on glycaemic regulation and weight changes in overweight patients with type 2 diabetes over 12 weeks.MethodsOverweight adults with type 2 diabetes (n = 120) were randomised 1:1 to two diet groups: time-restricted feeding (n = 60) or control (n = 60). Sixty patients participated in a 10-h restricted feeding treatment program (ad libitum feeding from 8:00 to 18:00 h; fasting between 18:00 and 8:00 h) for 12 weeks.ResultsHaemoglobin A1c and body weight decreased in the time-restricted feeding group (- 1.54% ± 0.19 and - 2.98 ± 0.43 kg, respectively) relative to the control group over 12 weeks (p < 0.001). Homeostatic model assessment of β-cell function and insulin resistance changed in the time-restricted feeding group (0.73 ± 0.21, p = 0.005; - 0.51 ± 0.08, p = 0.02, respectively) compared with the control group. The medication effect score, SF-12 score, and the levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol were improved in the time-restricted feeding group (- 0.66 ± 0.17, p = 0.006; 5.92 ± 1.38, p < 0.001; - 0.23 ± 0.08 mmol/L, p = 0.03; - 0.32 ± 0.07 mmol/L, p = 0.01; - 0.42 ± 0.13 mmol/L, p = 0.02, respectively) relative to the control group. High-density lipoprotein cholesterol was not significantly different between the two groups.ConclusionThese results suggest that 10-h restricted feeding improves blood glucose and insulin sensitivity, results in weight loss, reduces the necessary dosage of hypoglycaemic drugs and enhances quality of life. It can also offer cardiovascular benefits by reducing atherosclerotic lipid levels.Trial registrationThis study was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006371).

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Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.

Publications

Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.

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