Early or delayed time-restricted feeding prevents metabolic impact of obesity in mice

in Journal of Endocrinology
View More View Less
  • 1 Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
  • 2 Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia

Correspondence should be addressed to L Heilbronn: leonie.heilbronn@adelaide.edu.au

*(P Regmi and R Chaudhary contributed equally to this work)

Restricted access

Time-restricted feeding (TRF) initiated early during the dark phase prevents the metabolic consequences of a high-fat diet in rodent models. However, the metabolic consequences of delaying the initiation of TRF, akin to breakfast skipping in humans, is unclear. We assigned 8-week-old male C57BL/6J mice (n = 192) to chow or high-fat diet ad libitum (AL) for 4 weeks, before randomization to continue AL or 10 h of TRF, initiated at lights off (TRFe) or 4-h after lights off (TRFd) for a further 8 weeks. Oral glucose tolerance tests (1 g/kg), metabolic monitoring and body composition by echoMRI were performed, and tissues were collected at six time points. TRF reduced weight and fat mass vs AL, with a greater reduction in TRFe vs TRFd. TRF improved glucose tolerance and protected mice from high-fat diet-induced hepatosteatosis vs AL, with no difference between TRFe and TRFd. TRF increased the amplitude of Bmal1, Cry1, Per2, Nampt, and Nocturnin mRNA levels in liver. A phase delay in Bmal1, Cry1, Per2, Reverbα, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight benefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the translational potential of this dietary approach in humans.

 

Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 118 118 118
Full Text Views 87 87 87
PDF Downloads 28 28 28
  • Allison DB, Paultre F, Maggio C, Mezzitis N & Pi-Sunyer FX 1995 The use of areas under curves in diabetes research. Diabetes Care 18 245250. (https://doi.org/10.2337/diacare.18.2.245)

    • Search Google Scholar
    • Export Citation
  • Ando H, Ushijima K, Shimba S & Fujimura A 2016 Daily fasting blood glucose rhythm in male mice: a role of the circadian clock in the liver. Endocrinology 157 463469. (https://doi.org/10.1210/en.2015-1376)

    • Search Google Scholar
    • Export Citation
  • Andrikopoulos S, Blair AR, Deluca N, Fam BC & Proietto J 2008 Evaluating the glucose tolerance test in mice. American Journal of Physiology: Endocrinology and Metabolism 295 E1323E 1332. (https://doi.org/10.1152/ajpendo.90617.2008)

    • Search Google Scholar
    • Export Citation
  • Bergmeyer HU 1974 Methods of Enzymatic Analysis, p. 1. New York: Academic Press.

  • Bertoldo MJ, Listijono DR, Ho WJ, Riepsamen AH, Goss DM, Richani D, Jin XL, Mahbub S, Campbell JM & Habibalahi A et al. 2020 NAD(+) repletion rescues female fertility during reproductive aging. Cell Reports 30 1670 .e71681.e7. (https://doi.org/10.1016/j.celrep.2020.01.058)

    • Search Google Scholar
    • Export Citation
  • Bi H, Gan Y, Yang C, Chen Y, Tong X & Lu Z 2015 Breakfast skipping and the risk of type 2 diabetes: a meta-analysis of observational studies. Public Health Nutrition 18 30133019. (https://doi.org/10.1017/S1368980015000257)

    • Search Google Scholar
    • Export Citation
  • Bolli GB, De Feo P, De Cosmo S, Perriello G, Ventura MM, Calcinaro F, Lolli C, Campbell P, Brunetti P & Gerich JE 1984 Demonstration of a dawn phenomenon in normal human volunteers. Diabetes 33 11501153. (https://doi.org/10.2337/diab.33.12.1150)

    • Search Google Scholar
    • Export Citation
  • Bray MS, Tsai JY, Villegas-Montoya C, Boland BB, Blasier Z, Egbejimi O, Kueht M & Young ME 2010 Time-of-day-dependent dietary fat consumption influences multiple cardiometabolic syndrome parameters in mice. International Journal of Obesity 34 15891598. (https://doi.org/10.1038/ijo.2010.63)

    • Search Google Scholar
    • Export Citation
  • Canto C, Menzies KJ & Auwerx J 2015 NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metabolism 22 3153. (https://doi.org/10.1016/j.cmet.2015.05.023)

    • Search Google Scholar
    • Export Citation
  • Chaix A, Zarrinpar A, Miu P & Panda S 2014 Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metabolism 20 9911005. (https://doi.org/10.1016/j.cmet.2014.11.001)

    • Search Google Scholar
    • Export Citation
  • Chaix A, Lin T, Le HD, Chang MW & Panda S 2019 Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metabolism 29 303 .e4319.e4. (https://doi.org/10.1016/j.cmet.2018.08.004)

    • Search Google Scholar
    • Export Citation
  • Chance B, Schoener B, Oshino R, Itshak F & Nakase Y 1979 Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. Journal of Biological Chemistry 254 47644771.

    • Search Google Scholar
    • Export Citation
  • Christie S, Vincent AD, Li H, Frisby CL, Kentish SJ, O’Rielly R, Wittert GA & Page AJ 2018 A rotating light cycle promotes weight gain and hepatic lipid storage in mice. American Journal of Physiology: Gastrointestinal and Liver Physiology 315 G932G942. (https://doi.org/10.1152/ajpgi.00020.2018)

    • Search Google Scholar
    • Export Citation
  • Delahaye LB, Bloomer RJ, Butawan MB, Wyman JM, Hill JL, Lee HW, Liu AC, McAllan L, Han JC & van der Merwe M 2018 Time-restricted feeding of a high-fat diet in male C57BL/6 mice reduces adiposity but does not protect against increased systemic inflammation. Applied Physiology, Nutrition, and Metabolism 43 10331042. (https://doi.org/10.1139/apnm-2017-0706)

    • Search Google Scholar
    • Export Citation
  • Dunbar RIM 2017 Breaking bread: the functions of social eating. Adaptive Human Behavior and Physiology 3 198211. (https://doi.org/10.1007/s40750-017-0061-4)

    • Search Google Scholar
    • Export Citation
  • Duncan MJ, Smith JT, Narbaiza J, Mueez F, Bustle LB, Qureshi S, Fieseler C & Legan SJ 2016 Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet. Physiology and Behavior 167 19. (https://doi.org/10.1016/j.physbeh.2016.08.027)

    • Search Google Scholar
    • Export Citation
  • Eckel-Mahan KL, Patel VR, de Mateo S, Orozco-Solis R, Ceglia NJ, Sahar S, Dilag-Penilla SA, Dyar KA, Baldi P & Sassone-Corsi P 2013 Reprogramming of the circadian clock by nutritional challenge. Cell 155 14641478. (https://doi.org/10.1016/j.cell.2013.11.034)

    • Search Google Scholar
    • Export Citation
  • Ellacott KL, Morton GJ, Woods SC, Tso P & Schwartz MW 2010 Assessment of feeding behavior in laboratory mice. Cell Metabolism 12 1017. (https://doi.org/10.1016/j.cmet.2010.06.001)

    • Search Google Scholar
    • Export Citation
  • Espelund U, Hansen TK, Hojlund K, Beck-Nielsen H, Clausen JT, Hansen BS, Orskov H, Jorgensen JO & Frystyk J 2005 Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects. Journal of Clinical Endocrinology and Metabolism 90 741746. (https://doi.org/10.1210/jc.2004-0604)

    • Search Google Scholar
    • Export Citation
  • Estrella MA, Du J, Chen L, Rath S, Prangley E, Chitrakar A, Aoki T, Schedl P, Rabinowitz J & Korennykh A 2019 The metabolites NADP(+) and NADPH are the targets of the circadian protein Nocturnin (Curled). Nature Communications 10 2367. (https://doi.org/10.1038/s41467-019-10125-z)

    • Search Google Scholar
    • Export Citation
  • Galgani JE, Moro C & Ravussin E 2008 Metabolic flexibility and insulin resistance. American Journal of Physiology: Endocrinology and Metabolism 295 E1009E1017. (https://doi.org/10.1152/ajpendo.90558.2008)

    • Search Google Scholar
    • Export Citation
  • Gill S & Panda S 2015 A smartphone App reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metabolism 22 789798. (https://doi.org/10.1016/j.cmet.2015.09.005)

    • Search Google Scholar
    • Export Citation
  • Greenwell BJ, Trott AJ, Beytebiere JR, Pao S, Bosley A, Beach E, Finegan P, Hernandez C & Menet JS 2019 Rhythmic food intake drives rhythmic gene expression more potently than the hepatic circadian clock in mice. Cell Reports 27 649 .e5657.e5. (https://doi.org/10.1016/j.celrep.2019.03.064)

    • Search Google Scholar
    • Export Citation
  • Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M & Fitzpatrick JA et al. 2012 Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metabolism 15 848860. (https://doi.org/10.1016/j.cmet.2012.04.019)

    • Search Google Scholar
    • Export Citation
  • Hutchison AT, Regmi P, Manoogian ENC, Fleischer JG, Wittert GA, Panda S & Heilbronn LK 2019 Time-restricted feeding improves glucose tolerance in men at risk for Type 2 diabetes: a randomized crossover trial. Obesity 27 724732. (https://doi.org/10.1002/oby.22449)

    • Search Google Scholar
    • Export Citation
  • Jakubowicz D, Landau Z, Tsameret S, Wainstein J, Raz I, Ahren B, Chapnik N, Barnea M, Ganz T & Menaged M et al. 2019 Reduction in glycated hemoglobin and daily insulin dose alongside circadian clock upregulation in patients with type 2 diabetes consuming a three-meal diet: a randomized clinical trial. Diabetes Care 42 21712180. (https://doi.org/10.2337/dc19-1142)

    • Search Google Scholar
    • Export Citation
  • Kentish SJ, Hatzinikolas G, Li H, Frisby CL, Wittert GA & Page AJ 2018 Time-restricted feeding prevents ablation of diurnal rhythms in gastric vagal afferent mechanosensitivity observed in high-fat diet-induced obese mice. Journal of Neuroscience 38 50885095. (https://doi.org/10.1523/JNEUROSCI.0052-18.2018)

    • Search Google Scholar
    • Export Citation
  • Liu B, Page AJ, Hutchison AT, Wittert GA & Heilbronn LK 2019 Intermittent fasting increases energy expenditure and promotes adipose tissue browning in mice. Nutrition 66 3843. (https://doi.org/10.1016/j.nut.2019.03.015)

    • Search Google Scholar
    • Export Citation
  • Mistlberger RE 1994 Circadian food-anticipatory activity: formal models and physiological mechanisms. Neuroscience and Biobehavioral Reviews 18 171195. (https://doi.org/10.1016/0149-7634(9490023-x)

    • Search Google Scholar
    • Export Citation
  • Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL & Sinclair DA et al. 2014 The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Reports 6 836843. (https://doi.org/10.1016/j.celrep.2014.01.031)

    • Search Google Scholar
    • Export Citation
  • Poljsak B 2018 NAMPT-mediated NAD biosynthesis as the internal timing mechanism: in NAD+ world, time is running in its own way. Rejuvenation Research 21 210224. (https://doi.org/10.1089/rej.2017.1975)

    • Search Google Scholar
    • Export Citation
  • Ramsey KM, Mills KF, Satoh A & Imai S 2008 Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell 7 7888. (https://doi.org/10.1111/j.1474-9726.2007.00355.x)

    • Search Google Scholar
    • Export Citation
  • Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED & Lee C et al. 2009 Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324 651654. (https://doi.org/10.1126/science.1171641)

    • Search Google Scholar
    • Export Citation
  • Regmi P & Heilbronn LK 2020 Time-restricted eating: benefits, mechanisms, and challenges in translation. iScience 23 101161. (https://doi.org/10.1016/j.isci.2020.101161)

    • Search Google Scholar
    • Export Citation
  • Rudic RD, McNamara P, Curtis AM, Boston RC, Panda S, Hogenesch JB & Fitzgerald GA 2004 BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biology 2 e377. (https://doi.org/10.1371/journal.pbio.0020377)

    • Search Google Scholar
    • Export Citation
  • Sato S, Basse AL, Schonke M, Chen S, Samad M, Altintas A, Laker RC, Dalbram E, Barres R & Baldi P et al. 2019 Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metabolism 30 92 .e4110.e4. (https://doi.org/10.1016/j.cmet.2019.03.013)

    • Search Google Scholar
    • Export Citation
  • Serra M, Marongiu F, Pisu MG, Serra M & Laconi E 2019 Time-restricted feeding delays the emergence of the age-associated, neoplastic-prone tissue landscape. Aging 11 38513863. (https://doi.org/10.18632/aging.102021)

    • Search Google Scholar
    • Export Citation
  • Shimizu H, Hanzawa F, Kim D, Sun S, Laurent T, Umeki M, Ikeda S, Mochizuki S & Oda H 2018 Delayed first active-phase meal, a breakfast-skipping model, led to increased body weight and shifted the circadian oscillation of the hepatic clock and lipid metabolism-related genes in rats fed a high-fat diet. PLoS ONE 13 e0206669. (https://doi.org/10.1371/journal.pone.0206669)

    • Search Google Scholar
    • Export Citation
  • Srere PA 1969 Citrate synthase. In Methods in Enzymology, p. 5. Ed CaNO KaplanNew York: Academic Press.

  • Stromsdorfer KL, Yamaguchi S, Yoon MJ, Moseley AC, Franczyk MP, Kelly SC, Qi N, Imai S & Yoshino J 2016 NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Reports 16 18511860. (https://doi.org/10.1016/j.celrep.2016.07.027)

    • Search Google Scholar
    • Export Citation
  • Stubblefield JJ, Gao P, Kilaru G, Mukadam B, Terrien J & Green CB 2018 Temporal control of metabolic amplitude by nocturnin. Cell Reports 22 12251235. (https://doi.org/10.1016/j.celrep.2018.01.011)

    • Search Google Scholar
    • Export Citation
  • Sundaram S & Yan L 2016 Time-restricted feeding reduces adiposity in mice fed a high-fat diet. Nutrition Research 36 603611. (https://doi.org/10.1016/j.nutres.2016.02.005)

    • Search Google Scholar
    • Export Citation
  • Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E & Peterson CM 2018 Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metabolism 27 1212 .e31221.e3. (https://doi.org/10.1016/j.cmet.2018.04.010)

    • Search Google Scholar
    • Export Citation
  • Tschop MH, Speakman JR, Arch JR, Auwerx J, Bruning JC, Chan L, Eckel RH, Farese Jr RV, Galgani JE & Hambly C et al. 2011 A guide to analysis of mouse energy metabolism. Nature Methods 9 5763. (https://doi.org/10.1038/nmeth.1806)

    • Search Google Scholar
    • Export Citation
  • Velingkaar N, Mezhnina V, Poe A, Makwana K, Tulsian R & Kondratov RV 2020 Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction. Aging Cell 19 e13138. (https://doi.org/10.1111/acel.13138)

    • Search Google Scholar
    • Export Citation
  • Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD & Panda S 2009 Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. PNAS 106 2145321458. (https://doi.org/10.1073/pnas.0909591106)

    • Search Google Scholar
    • Export Citation
  • Weir JB 1949 New methods for calculating metabolic rate with special reference to protein metabolism. Journal of Physiology 109 19. (https://doi.org/10.1113/jphysiol.1949.sp004363)

    • Search Google Scholar
    • Export Citation
  • Wilkinson MJ, Manoogian ENC, Zadourian A, Lo H, Fakhouri S, Shoghi A, Wang X, Fleischer JG, Navlakha S & Panda S et al. 2020 Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metabolism 31 92 .e5104.e5. (https://doi.org/10.1016/j.cmet.2019.11.004)

    • Search Google Scholar
    • Export Citation
  • Woodie LN, Luo Y, Wayne MJ, Graff EC, Ahmed B, O’Neill AM & Greene MW 2018 Restricted feeding for 9h in the active period partially abrogates the detrimental metabolic effects of a Western diet with liquid sugar consumption in mice. Metabolism: Clinical and Experimental 82 113. (https://doi.org/10.1016/j.metabol.2017.12.004)

    • Search Google Scholar
    • Export Citation
  • Yasumoto Y, Hashimoto C, Nakao R, Yamazaki H, Hiroyama H, Nemoto T, Yamamoto S, Sakurai M, Oike H & Wada N et al. 2016 Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice. Metabolism: Clinical and Experimental 65 714727. (https://doi.org/10.1016/j.metabol.2016.02.003)

    • Search Google Scholar
    • Export Citation