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Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

ABSTRACT: Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (?13%) and IMF-LFD (?18%) had significantly lower body weights than the HFD. Body fat was also lower (?40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (?12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (?50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (?22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (?55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (?19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (?65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

SUBMITTER: Gotthardt JD

PROVIDER: S-EPMC4733124 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

Gotthardt Juliet D JD Verpeut Jessica L JL Yeomans Bryn L BL Yang Jennifer A JA Yasrebi Ali A Roepke Troy A TA Bello Nicholas T NT

Endocrinology 20151214 2

Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD ...[more]

PMID: 26653760

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Project description:BackgroundIntermittent fasting (IF) is an increasingly popular approach to dietary control that focuses on the timing of eating rather than the quantity and content of caloric intake. IF practitioners typically seek to improve their weight and other health factors. Millions of practitioners have turned to purpose-built mobile apps to help them track and adhere to their fasts and monitor changes in their weight and other biometrics.ObjectiveThis study aimed to quantify user retention, fasting patterns, and weight loss by users of 2 IF mobile apps. We also sought to describe and model starting BMI, amount of fasting, frequency of weight tracking, and other demographics as correlates of retention and weight change.MethodsWe assembled height, weight, fasting, and demographic data of adult users (ages 18-100 years) of the LIFE Fasting Tracker and LIFE Extend apps from 2018 to 2020. Retention for up to 52 weeks was quantified based on recorded fasts and correlated with user demographics. Users who provided height and at least 2 readings of weight and whose first fast and weight records were contemporaneous were included in the weight loss analysis. Fasting was quantified as extended fasting hours (EFH; hours beyond 12 in a fast) averaged per day (EFH per day). Retention was modeled using a Cox proportional hazards regression. Weight loss was analyzed using linear regression.ResultsA total of 792,692 users were followed for retention based on 26 million recorded fasts. Of these, 132,775 (16.7%) users were retained at 13 weeks, 54,881 (6.9%) at 26 weeks, and 16,478 (2.1%) at 52 weeks, allowing 4 consecutive weeks of inactivity. The survival analysis using Cox regression indicated that retention was positively associated with age and exercise and negatively associated with stress and smoking. Weight loss in the qualifying cohort (n=161,346) was strongly correlated with starting BMI and EFH per day, which displayed a positive interaction. Users with a BMI ≥40 kg/m2 lost 13.9% of their starting weight by 52 weeks versus a slight weight gain on average for users with starting BMI <23 kg/m2. EFH per day was an approximately linear predictor of weight loss. By week 26, users lost over 1% of their starting weight per EFH per day on average. The regression analysis using all variables was highly predictive of weight change at 26 weeks (R2=0.334) with starting BMI and EFH per day as the most significant predictors.ConclusionsIF with LIFE mobile apps appears to be a sustainable approach to weight reduction in the overweight and obese population. Healthy weight and underweight individuals do not lose much weight on average, even with extensive fasting. Users who are obese lose substantial weight over time, with more weight loss in those who fast more.

Project description:Background/objectivesAlternate day fasting (ADF) is a subtype of intermittent fasting and is defined as a continuous sequence of a fast day (100% energy restriction, zero calories) and a feed day (ad libitum food consumption), resulting in roughly 36-h fasting periods. Previous studies demonstrated weight reductions and improvements of cardiovascular risk factors with ADF in obese subjects. However, rigorous data on potential endocrine, metabolic and cardiovascular effects, besides weight loss, are lacking. Therefore we aim to investigate the short- and mid- to long-term clinical and molecular effects of ADF in healthy non-obese subjects.MethodsWe will perform a prospective cohort study with an embedded randomized controlled trial (RCT) including 90 healthy subjects. Thirty of them will have performed ADF for at least 6 months (mid-term group). Sixty healthy subjects without a particular diet before enrolment will serve as the control group. These subjects will be 1:1 randomized to either continuing their current diet or performing ADF for 4 weeks. All subjects will undergo study procedures that will be repeated in RCT participants after 4 weeks. These procedures will include assessment of outcome parameters, dual-energy X-ray absorptiometry, measurement of endothelial function, an oral glucose tolerance test, 24-h blood pressure measurement, retinal vessel analysis, echocardiography and physical activity measurement by an accelerometer. Blood, sputum, buccal mucosa and faeces will be collected for laboratory analyses. Participants in the RCT will wear a continuous glucose monitor to verify adherence to the study intervention.Planned outcomesThe aim of this project is to investigate the effects of ADF on human physiology and molecular cellular processes. This investigation should gain in-depth mechanistic insights into the concept of ADF and form the basis for larger subsequent cohort recruitment and consecutive intervention studies.Trial registrationNCT02673515; registered 24 November 2015. Current protocol date/version: 7 February 2017/version 1.8.

Dataset Information

Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

Publications

Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

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