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• W2806819290 abstract "The prevalence of diabetes is on the rise, leading to astronomical increases in healthcare costs. In this issue of Cell Metabolism, Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27 (this issue): 1212-1221Abstract Full Text Full Text PDF PubMed Scopus (604) Google Scholar report improved metabolic outcomes even without weight loss. The trick? Eat early and for only 6 hr of the day. The prevalence of diabetes is on the rise, leading to astronomical increases in healthcare costs. In this issue of Cell Metabolism, Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27 (this issue): 1212-1221Abstract Full Text Full Text PDF PubMed Scopus (604) Google Scholar report improved metabolic outcomes even without weight loss. The trick? Eat early and for only 6 hr of the day. Dietary interventions, including calorie restriction (CR), have been at the forefront of the study of aging and lifespan extension. Generally speaking, CR refers to a reduction in the number of calories consumed over the course of a day. Since its inception, the field has expanded in attempts to determine how and why CR works. To date, several variations of daily dietary regimens have been described and referred to as “intermittent fasting,” with each variation incorporating a perturbation of typical eating habits such as the time of day for eating, the length of time between meals, and prolonged periods of fasting. Recently, there has been great interest in a type of intermittent fasting called time-restricted feeding (TRF). In this issue of Cell Metabolism, Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27 (this issue): 1212-1221Abstract Full Text Full Text PDF PubMed Scopus (604) Google Scholar utilize early TRF (or eTRF), restricting meal time to 6 hr in the early part of the day, to challenge the concept that the loss of body weight is required to confer metabolic benefits. Humans usually have daily intermittent periods of feeding along with periods of fasting, which typically last 6–8 hr, coinciding with sleep. An early TRF combines daily fasting and the alignment of meals with normal circadian and metabolic rhythms. The goal is to increase the daily fasting period, causing the body to shift to alternative metabolic phases that rely less on glucose and more on ketone sources, resulting in pleiotropic benefits often sustained long after the diet regimen has ceased (Longo and Panda, 2016Longo V.D. Panda S. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan.Cell Metab. 2016; 23: 1048-1059Abstract Full Text Full Text PDF PubMed Scopus (452) Google Scholar). To date, most of what we have learned about TRF comes from rodent studies. When given a high-fat diet, mice will graze and eat throughout the day and night. Yet restricting access to the same diet to just a 12-hr period overnight, during their active time, improved metabolic health without actually decreasing caloric intake (Hatori et al., 2012Hatori M. Vollmers C. Zarrinpar A. DiTacchio L. Bushong E.A. Gill S. Leblanc M. Chaix A. Joens M. Fitzpatrick J.A. et al.Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.Cell Metab. 2012; 15: 848-860Abstract Full Text Full Text PDF PubMed Scopus (1190) Google Scholar), clear evidence that circadian rhythms and meal timing are inextricably linked. Similarly, there is a circadian rhythm to metabolic processes including insulin secretion, and when disrupted, it can lead to weight gain in mice (Arble et al., 2009Arble D.M. Bass J. Laposky A.D. Vitaterna M.H. Turek F.W. Circadian timing of food intake contributes to weight gain.Obesity (Silver Spring). 2009; 17: 2100-2102Crossref PubMed Scopus (678) Google Scholar) and humans (McHill and Wright, 2017McHill A.W. Wright Jr., K.P. Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease.Obes. Rev. 2017; 18: 15-24Crossref PubMed Scopus (179) Google Scholar). Thus, timing the majority of calorie consumption to coincide with the time that the endocrine system is most responsive may maximize the ability of the body to process the food. In fact, a cross-sectional study in humans reported that it is not the hour on the clock that is significant but the timing of food intake relative to melatonin release (McHill et al., 2017McHill A.W. Phillips A.J. Czeisler C.A. Keating L. Yee K. Barger L.K. Garaulet M. Scheer F.A. Klerman E.B. Later circadian timing of food intake is associated with increased body fat.Am. J. Clin. Nutr. 2017; 106: 1213-1219PubMed Scopus (217) Google Scholar). The leaner individuals consumed a greater proportion of their daily calories in the early circadian clock relative to those with higher body fat. Interestingly, there was no association with clock hour, only relative to the individuals’ timing of melatonin release (McHill et al., 2017McHill A.W. Phillips A.J. Czeisler C.A. Keating L. Yee K. Barger L.K. Garaulet M. Scheer F.A. Klerman E.B. Later circadian timing of food intake is associated with increased body fat.Am. J. Clin. Nutr. 2017; 106: 1213-1219PubMed Scopus (217) Google Scholar). Sutton et al. report here a TRF study of eight pre-diabetic men, who were overweight and borderline hypertensive, that participated in two study conditions, each lasting 5 weeks: (1) a controlled feeding condition, allowing meals over a 12-hr period, and (2) an eTRF condition, which limited meals to be eaten periodically over just 6 hr, completing all meals by 3 p.m. Investigators maintained oversight of all meals and matched caloric intake across study arms to guard against weight loss. The level of compliance reported from the subjects is most remarkable. This well-controlled cross-over study provides evidence that the beneficial effects of eTRF are not solely dependent on weight loss. Rather, decreased blood pressure, oxidative stress, and insulin, and improved insulin sensitivity, are linked to circadian rhythms and meal timing, potentially providing a more tangible target for intervention strategies. Very recently, Delahaye et al., 2018Delahaye L.B. Bloomer R.J. Butawan M.B. Wyman J.M. Hill J.L. Lee H.W. Liu A.C. McAllan L. Han J.C. van der Merwe M. Time-restricted feeding of a high fat diet in C57BL/6 male mice reduces adiposity, but does not protect against increased systemic inflammation.Appl. Physiol. Nutr. Metab. 2018; (Published online May 2, 2018)https://doi.org/10.1139/apnm-2017-0706Crossref PubMed Scopus (31) Google Scholar provided additional evidence that, in mice, eating early within the circadian cycle elicits the greatest benefits. Although TRF of mice on a high-fat diet provided some benefits, those in the early eating group gained less weight and maintained better insulin sensitivity than the late eaters. Additionally, markers of inflammation were improved in both TRF groups, which did not occur in the Sutton report, a difference that may be attributed to a species-specific effect or the response to a high-fat diet. The increase in triglycerides observed under the eTRF condition might give pause as high levels are clinically linked to heart disease. However, several studies have reported decreased triglyceride levels with extended fasting time (Tinsley and La Bounty, 2015Tinsley G.M. La Bounty P.M. Effects of intermittent fasting on body composition and clinical health markers in humans.Nutr. Rev. 2015; 73: 661-674Crossref PubMed Scopus (174) Google Scholar). So this outcome deserves further investigation. Similarly, mechanistic questions remain to be addressed (Figure 1). Although body weight remained the same, what happened to body composition? It has been our experience that metabolic intervention studies can result in important changes in body composition (i.e., lean versus fat body mass) that do not alter body weight (Ortega-Molina et al., 2015Ortega-Molina A. Lopez-Guadamillas E. Mattison J.A. Mitchell S.J. Muñoz-Martin M. Iglesias G. Gutierrez V.M. Vaughan K.L. Szarowicz M.D. González-García I. et al.Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.Cell Metab. 2015; 21: 558-570Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). It would be important to know if there were indeed changes in body composition that could be the driving factor behind the beneficial effects seen. Likewise, what is the impact of eTRF on the microbiome? Lately it seems that no metabolic story is complete without information on changes in the gut microbiome; is their clock “in sync” with ours? We know the microbiota is dynamic and is linked to metabolism, immune function, obesity, and a host of diseases. It, too, has a circadian fluctuation that can be disrupted by diet-induced obesity. In fact, TRF restores the flora cyclicity and may protect against metabolic disease in mice (Zarrinpar et al., 2014Zarrinpar A. Chaix A. Yooseph S. Panda S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome.Cell Metab. 2014; 20: 1006-1017Abstract Full Text Full Text PDF PubMed Scopus (483) Google Scholar). We still have much to learn about the role of gut microbes in this complex interconnected system. In closing, the current report provides compelling new evidence that TRF interventions can be useful clinical tools. As we move forward in our understanding of how TRF interventions benefit health, more questions emerge, from basic mechanisms to implementation for improvements of clinical conditions or sustained good health. For those teetering on the edge of type 2 diabetes, improved insulin responsiveness and regulation of metabolism might best be controlled by watching the clock and not the scale. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with PrediabetesSutton et al.Cell MetabolismMay 10, 2018In BriefSutton et al. conduct the first supervised controlled feeding trial to test whether intermittent fasting has benefits in humans in the absence of weight loss. Prediabetic men following a form of intermittent fasting called early time-restricted feeding improved their insulin sensitivity, blood pressure, and oxidative stress levels without losing weight. Full-Text PDF Open Archive" @default.
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• W2806819290 title "Watch the Clock, Not the Scale" @default.
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