A rotating light cycle promotes weight gain and hepatic lipid storage in mice

Christie, Stewart; Vincent, Andrew; Li, Hui; Frisby, Claudine L.; Kentish, Stephen J.; O’Rielly, Rebecca; Wittert, Gary; Page, Amanda J.

doi:10.1152/ajpgi.00020.2018

Cited by 30 publications

(33 citation statements)

References 58 publications

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“…Desynchronization of circadian clocks by altering the timing of food intake can lead to uncoupling of peripheral clocks with the central clock which subsequently leads to the development of metabolic disorders . For example, in the mice from the current study fatty liver was observed in the SLD‐RL mice to the same level as that observed in the HFD‐mice . The adverse effects of desynchronization of circadian clocks are not limited to metabolic syndrome, with disruption of the circadian system an important contributor to a number of pathological diseases including various gastrointestinal disorders such as gastrointestinal motility disorders .…”

Section: Discussionmentioning

confidence: 64%

“…Weight gain and gonadal fat pad mass have been reported previously . Briefly, there was no difference in the body weight of the mice randomly allocated to the 4 different groups (Table ).…”

Section: Resultsmentioning

confidence: 79%

“…For the RL cycle mice, this occurred 24 hours after exposure to the normal light phase to be consistent with the control NL mice. Twenty‐four hour food intake, energy expenditure, respiratory quotient, and movement have been previously reported for these mice …”

Section: Methodsmentioning

confidence: 79%

“…After a 4 week diet acclimatization period, mice were further randomized into two groups per diet and exposed to either a normal light cycle (NL; n = 120) or a rotating light cycle (RL; n = 128). These light cycles have been described in detail previously . Briefly, a NL cycle was a 12 hour light: 12 hour dark light cycle with lights on at 0600 (Zeitgeber [ZT] 0).…”

Section: Methodsmentioning

confidence: 99%

“…These light cycles have been described in detail previously. 17 Briefly, a NL cycle was a 12 hour light: 12 hour dark light cycle with lights on at 0600 (Zeitgeber [ZT] 0). A RL cycle was defined as 3 days of NL cycle followed by 4 days of reverse light cycle, with lights on at 1800 (ZT12).…”

Section: Animals and Rotating Light Protocolmentioning

confidence: 99%

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Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

Kentish

Christie

Vincent

et al. 2019

Neurogastroenterology Motil

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Background Gastric vagal afferents (GVAs) respond to mechanical stimulation, initiating satiety. These afferents exhibit diurnal fluctuations in mechanosensitivity, facilitating food intake during the dark phase in rodents. In humans, desynchrony of diurnal rhythms (eg, shift work) is associated with a higher risk of obesity. To test the hypothesis that shift work disrupts satiety signaling, the effect of a rotating light cycles on diurnal rhythms in GVA mechanosensitivity in lean and high‐fat diet (HDF)‐induced obese mice was determined. Methods Male C57BL/6 mice were fed standard laboratory diet (SLD) or HFD for 12 weeks. After 4 weeks, mice were randomly allocated to a normal light (NL; 12 hour light: 12 hour dark; lights on at zeitgeber time [ZT] 0) or rotating light (RL; 3‐day NL cycle, 4‐day reversed light cycle [lights on: ZT12] repeated) cycle for 8 weeks. At week 12, eight mice from each group were housed in metabolic cages. After 12 weeks, ex vivo GVA recordings were taken at 3 hour intervals starting at ZT0. Key Results SLD‐RL and HFD‐RL gained more weight compared to SLD‐NL and HFD‐NL mice, respectively. Gonadal fat pad mass was higher in SLD‐RL compared to SLD‐NL mice. In SLD‐NL mice, tension and mucosal receptor mechanosensitivity exhibited diurnal rhythms with a peak at ZT9. These rhythms were lost in SLD‐RL, HFD‐NL, and HFD‐RL mice and associated with dampened diurnal rhythms in food intake. Conclusions & Inferences GVA diurnal rhythms are susceptible to disturbances in the light cycle and/or the obese state. This may underpin the observed changes in feeding behavior.

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Section: Discussionmentioning

confidence: 64%

“…Weight gain and gonadal fat pad mass have been reported previously . Briefly, there was no difference in the body weight of the mice randomly allocated to the 4 different groups (Table ).…”

Section: Resultsmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Animals and Rotating Light Protocolmentioning

confidence: 99%

See 3 more Smart Citations

Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

Kentish

Christie

Vincent

et al. 2019

Neurogastroenterology Motil

Self Cite

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Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD

et al. 2022

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This work aimed to investigate the role of nuclear factor peroxisome proliferator-activated receptor α (PPARα) in modi cation of circadian clock and their relevance to development of nonalcoholic fatty liver disease (NAFLD). Both male wild-type (WT) and Pparα-null (KO) mice treated with high-fat diet (HFD) were used to explore the effect of PPARα and lipid diet on the circadian clock. PPARα humanized (hPPARα) mice were treated with PPARα agonist feno brate to reveal the hPPARα-dependence of circadian locomotor output cycles kaput (CLOCK) down-regulation. Hepatocytes were challenged with oleic acid and WY-14643 to verify the action of PPARα in down-regulating CLOCK and lipid accumulation. Strongest NAFLD developed in mice fed 45%HFD and it was inhibited in WT mice. The night/day diet consumption ratio was inhibited more in WT mice than that in KO mice on HFD. The core circadian factor CLOCK was down-regulated by HFD in both WT and KO mice in the liver, not in the hypothalamus. More interestingly, hepatic CLOCK was down-regulated by basal PPARα and activated hPPARα in dosedependence of feno brate. According with the in vivo experiments, CLOCK down-regulation by activated PPARα was involved in inhibition of lipid accumulation in hepatocytes. Down-regulation of hepatic CLOCK by basal PPARα contributes to tolerance against development of NAFLD. Inhibition of CLOCK by activated PPARα is involved in inhibition of NAFLD by PPARα agonists.

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Time-Restricted Eating: Benefits, Mechanisms, and Challenges in Translation

2020

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Eating out of phase with daily circadian rhythms induces metabolic desynchrony in peripheral metabolic organs and may increase chronic disease risk. Timerestricted eating (TRE) is a dietary approach that consolidates all calorie intake to 6-to 10-h periods during the active phase of the day, without necessarily altering diet quality and quantity. TRE reduces body weight, improves glucose tolerance, protects from hepatosteatosis, increases metabolic flexibility, reduces atherogenic lipids and blood pressure, and improves gut function and cardiometabolic health in preclinical studies. This review discusses the importance of meal timing on the circadian system, the metabolic health benefits of TRE in preclinical models and humans, the possible mechanisms of action, the challenges we face in implementing TRE in humans, and the possible consequences of delaying initiation of TRE. REGULATION OF CENTRAL AND PERIPHERAL CLOCK MACHINERYCircadian rhythms are ubiquitous periodic oscillations in internal biological process that direct behavior and metabolism such as hormonal signaling, body temperature, nutrient absorption, and metabolism (Dongen 2017;Espelund et al., 2005;Panda et al., 2002;Reppert and Weaver, 2002). At the molecular level, circadian rhythms arise from tightly controlled autonomous interlocked genetic transcriptional feedback loop that involves circadian locomotor output cycles kaput (clock) and brain and muscle ARNT like protein 1 (bmal1) as positive transcriptional factors for period (per1, per2, per3) and cryptochrome (cry1, cry2) genes (extensively reviewed in Hastings et al., 2018). The translation products of per and cry dimerize and act as negative regulators by inhibiting clock and bmal1. An additional feedback loop involves the transcriptional regulation of bmal1 by retinoic acid related orphan receptor (rora) and nuclear receptor subfamily 1, group D, member 1(rev-erba). One cycle of this feedback loop takes ~24 h and is the basis of circadian rhythms in many organisms. The suprachiasmatic nucleus (SCN) is considered the master regulator of circadian rhythms and is primarily entrained by the light-dark cycle. This feedback loop also operates in

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A rotating light cycle promotes weight gain and hepatic lipid storage in mice

Cited by 30 publications

References 58 publications

Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD

Time-Restricted Eating: Benefits, Mechanisms, and Challenges in Translation

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