The hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression

Fougeray, Tiffany; Polizzi, Arnaud; Régnier, Marion; Fougerat, Anne; Ellero‐Simatos, Sandrine; Lippi, Yannick; Smati, Sarra; Lasserre, Frédèric; Tramunt, Blandine; Huillet, Marine; Dopavogui, Léonie; Salvi, Juliette; Nédélec, Emmanuelle; Gigot, Vincent; Smith, Lorraine; Naylies, Claire; Sommer, Caroline; Haas, Joel T.; Wahli, Walter; Duez, Hélène; Gourdy, Pierre; Gamet-Payrastre, Laurence; Bénani, Alexandre; Burnol, Anne-Françoise; Loiseau, Nicolas; Postic, Catherine; Montagner, Alexandra; Guillou, Hervé

doi:10.1016/j.celrep.2022.110674

Cited by 12 publications

(16 citation statements)

References 69 publications

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“…For example, the phase of the circadian clock in the liver in mice shifts to align with feeding behavior in LRF mice. The shift in the liver circadian clock relies on the presence of hepatic insulin receptors ( Fougeray et al, 2022 ). Tissues that have a limited phase shift like the heart and kidney are continuously functioning and gene expression may not shift as much as a result while the liver is highly metabolic and responsive to the presence of food, functioning to homeostatically regulate blood glucose, and may shift gene expression for appropriate food utilization.…”

Section: Discussionmentioning

confidence: 99%

“…SCN regulated pathways including neurohumoral signaling (autonomic, glucocorticoids, insulin signaling, etc.) and daily changes in core body temperature have been shown to contribute ( Balsalobre et al, 2000 ; Terazono et al, 2003 ; Buhr et al, 2010 ; Fougeray et al, 2022 ). One possible entrainment factor is glucocorticoid signaling.…”

Section: Introductionmentioning

confidence: 99%

“…Glucocorticoid receptor signaling may play a role in the apparent slow phase shifts observed in the circadian gene expression of peripheral tissues in response to LRF (7–10 days, liver) ( Damiola et al, 2000 ). Another study demonstrated that circadian gene expression in the liver requires a functional insulin receptor to entrain the circadian clock mechanism to LRF ( Fougeray et al, 2022 ). These data suggest an important role for insulin signaling/hepatocyte insulin sensitivity in regulating the liver circadian clock with important implications for maintaining blood glucose homeostasis, as well as how circadian disruption could effect metabolic homeostasis and contribute to metabolic disorders (e.g., metabolic disease, obesity and diabetes) ( Fougeray et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Another study demonstrated that circadian gene expression in the liver requires a functional insulin receptor to entrain the circadian clock mechanism to LRF ( Fougeray et al, 2022 ). These data suggest an important role for insulin signaling/hepatocyte insulin sensitivity in regulating the liver circadian clock with important implications for maintaining blood glucose homeostasis, as well as how circadian disruption could effect metabolic homeostasis and contribute to metabolic disorders (e.g., metabolic disease, obesity and diabetes) ( Fougeray et al, 2022 ). Future studies may identify tissue specific signaling mechanisms that regulate the circadian clock to alterations in the timing of feeding.…”

Section: Introductionmentioning

confidence: 99%

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Time Restricted Feeding to the Light Cycle Dissociates Canonical Circadian Clocks and Physiological Rhythms in Heart Rate

Schroder

Delisle

2022

Front. Pharmacol.

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Circadian rhythms are approximate 24-h biological cycles that optimize molecular and physiological functions to predictable daily environmental changes in order to maintain internal and organismal homeostasis. Environmental stimuli (light, feeding, activity) capable of altering the phase of molecular rhythms are important tools employed by circadian biologists to increase understanding of the synchronization of circadian rhythms to the environment and to each other within multicellular systems. The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus is largely responsive to light and is thought to entrain the phase of peripheral clocks via neurohumoral signals. Mice are nocturnal and consume most of their food during the dark cycle. Early studies demonstrated that altered metabolic cues in the form of time restricted feeding, specifically, feeding mice during the light cycle, resulted in an uncoupling of molecular clocks in peripheral tissues with those from the SCN. These studies showed as much as a 12-h shift in gene expression in some peripheral tissues but not others. The shifts occurred without corresponding changes in the central clock in the brain. More recent studies have demonstrated that changes in cardiac physiology (heart rate, MAP) in response to time of food intake occur independent of the cardiac molecular clock. Understanding differences in the physiology/function and gene expression in other organs both independently and in relation to the heart in response to altered feeding will be important in dissecting the roles of the various clocks throughout the body, as well as, understanding their links to cardiovascular pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Time Restricted Feeding to the Light Cycle Dissociates Canonical Circadian Clocks and Physiological Rhythms in Heart Rate

Schroder

Delisle

2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…In the liver, insulin-mediated activation of the PI3K/AKT pathway restrains gluconeogenesis, glycogenolysis and stimulates lipogenesis and glycogen synthesis [53,54], as well as normal function of the hepatocyte insulin receptor is required to maintain the liver clock and associated circadian gene expression patterns [55]. The hepatic lipid storage capacity is determined through the harmonization of several processes including DNL, fatty acid uptake, triglyceride synthesis, fatty acid oxidation, and triglyceride export.…”

Section: Role Of Pi3k/akt In Hepatic Tissuementioning

confidence: 99%