Differential effect of fructose on fat metabolism and clock gene expression in hepatocytes vs . myotubes

Chapnik, Nava; Rozenblit-Susan, Sigal; Genzer, Yoni; Froy, Oren

doi:10.1016/j.biocel.2016.05.019

Cited by 7 publications

(13 citation statements)

References 21 publications

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“…Given the critical role of CRY1 in the circadian clock, it would be of great interest to study the impact of fructose on the molecular circadian clock in both cells and whole animals. In fact, a study from the Froy group showed that fructose impairs the molecular circadian clock in hepatocytes while increasing the amplitude of circadian gene oscillations in muscle cells [ 32 ]. It is tantalizing to hypothesize that fructose modulates the circadian clock via the regulation of CRY1 turnover.…”

Section: Discussionmentioning

confidence: 99%

DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1

et al. 2020

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Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose. Depletion and overexpression of Ddb1 showed opposite effects on the ChREBPα stability in hepatocytes. We next tested the impact of hepatic Ddb1 deficiency on the fructose-induced ChREBP pathway. After 3-week high-fructose diet feeding, both Ddb1 liver-specific knockout and AAV-TBG-Cre-injected Ddb1 flox/flox mice showed significantly reduced ChREBPα, lipogenic enzymes, as well as triglycerides in the liver. Mechanistically, DDB1 stabilizes ChREBPα through CRY1, a known ubiquitination target of DDB1 E3 ligase. Finally, overexpression of a degradation-resistant CRY1 mutant (CRY1–585KA) reduces ChREBPα and its target genes in the mouse liver following high-fructose diet feeding. Our data revealed DDB1 as an intracellular sensor of fructose intake to promote hepatic de novo lipogenesis and liver steatosis by stabilizing ChREBPα in a CRY1-dependent manner.

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Section: Discussionmentioning

confidence: 99%

DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1

et al. 2020

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“…At the liver level, fructose inhibits the circadian rhythm of Bmal-1 and causes a delay in the peak expression of Per-1 and Clock in about 9 and 2 hours, respectively. At the same time, it reduces the amplitude of Bmal-1 and Per-1 expression and decreases the rate of phosphorylation of pAMPK and p-ACC, critical enzymes in the inhibition of translocation of fatty acids to mitochondria, and its subsequent β -oxidation, finally inducing the synthesis of lipids in the liver [ 68 ]. At the muscle level, fructose induces an increase in the amplitude of oscillation of the Per-1 and Bmal-1 genes and an increase in the phosphorylation ratio of pAMPK, p-ACC, and the expression of transcription factor PPAR α (stimulator of β -oxidation) which results in an inhibition of translocation of fatty acids to the mitochondria and thereby increasing the availability of substrate for β -oxidation [ 68 ].…”

Section: A New Role Of Melatonin: Inhibiting the Metabolic Effectsmentioning

confidence: 99%

“…At the same time, it reduces the amplitude of Bmal-1 and Per-1 expression and decreases the rate of phosphorylation of pAMPK and p-ACC, critical enzymes in the inhibition of translocation of fatty acids to mitochondria, and its subsequent β -oxidation, finally inducing the synthesis of lipids in the liver [ 68 ]. At the muscle level, fructose induces an increase in the amplitude of oscillation of the Per-1 and Bmal-1 genes and an increase in the phosphorylation ratio of pAMPK, p-ACC, and the expression of transcription factor PPAR α (stimulator of β -oxidation) which results in an inhibition of translocation of fatty acids to the mitochondria and thereby increasing the availability of substrate for β -oxidation [ 68 ]. This previous metabolic desynchronization adds the observation in patients treated with fructose-sweetened beverages, where the area under the curve during 24 hours (AUC) of plasma glucose and insulin levels is lower than those of patients who drank glucose-sweetened beverages.…”

Section: A New Role Of Melatonin: Inhibiting the Metabolic Effectsmentioning

confidence: 99%

“…Fructose induces lipogenesis via SREBP-1c stimulation [ 26 , 29 ], hypertension [ 8 , 10 , 25 – 27 , 33 , 34 ], gluconeogenesis [ 23 , 29 ], hyperuricemia, and reactive oxygen species (ROS) [ 8 , 28 ]. Besides, it induces chrono-disruption [ 67 , 68 ], and the impairment expression of clock genes modifies the circadian output of PGC1 α , PPAR α , NRF, SIRT1, and UCP1 [ 1 , 48 – 50 ]. The molecular inhibition of PGC1 α , PPAR α , NRF, SIRT1, and UCP1 by fructose [ 8 , 22 , 26 , 28 , 29 , 32 , 82 , 83 ] can be reverted by melatonin exposition [ 44 , 51 , 54 – 56 ].…”

Section: Figurementioning

confidence: 99%

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Potential Crosstalk between Fructose and Melatonin: A New Role of Melatonin—Inhibiting the Metabolic Effects of Fructose

Valenzuela-Melgarejo

Caro-Díaz

Cabello-Guzmán

2018

International Journal of Endocrinology

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Increased consumption of energy-dense foods such as fructose-rich syrups represents one of the significant, growing concerns related to the alarming trend of overweight, obesity, and metabolic disorders worldwide. Metabolic pathways affected by fructose involve genes related to lipogenesis/lipolysis, beta-oxidation, mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation pathways, or altering of circadian production of insulin and leptin. Moreover, fructose can be a risk factor during pregnancy elevating the risk of preterm delivery, hypertension, and metabolic impairment of the mother and fetus. Melatonin is a chronobiotic and homeostatic hormone that can modulate the harmful effects of fructose via clock gene expression and metabolic pathways, modulating the expression of PPARγ, SREBF-1 (SREBP-1), hormone-sensitive lipase, C/EBP-α genes, NRF-1, PGC1α, and uncoupling protein-1. Moreover, this hormone has the capacity in the rat of reverting the harmful effects of fructose, increasing the body weight and weight ratio of the liver, and increasing the body weight and restoring the glycemia from mothers exposed to fructose. The aim of this review is to show the potential crosstalk between fructose and melatonin and their potential role during pregnancy.

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“…Fructose and glucose are characterized by the same chemical formula; however, they differ in structure and metabolism. In hepatocytes, fructose led to disrupted Bmal1 mRNA expression and delayed the expression of Per1 mRNA (Chapnik et al , 2016). In myotubes, fructose induced a higher amplitude of Per1 and Bmal1 mRNA expression and delayed rhythms of Per1 , Bmal1 , and Clock (Chapnik et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming

Sassone–Corsi

2022

EMBO Reports

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Food intake profoundly affects systemic physiology. A large body of evidence has indicated a link between food intake and circadian rhythms, and ~24-h cycles are deemed essential for adapting internal homeostasis to the external environment. Circadian rhythms are controlled by the biological clock, a molecular system remarkably conserved throughout evolution. The circadian clock controls the cyclic expression of numerous genes, a regulatory program common to all mammalian cells, which may lead to various metabolic and physiological disturbances if hindered. Although the circadian clock regulates multiple metabolic pathways, metabolic states also provide feedback on the molecular clock. Therefore, a remarkable feature is reprogramming by nutritional challenges, such as a high-fat diet, fasting, ketogenic diet, and caloric restriction. In addition, various factors such as energy balance, histone modifications, and nuclear receptor activity are involved in the remodeling of the clock. Herein, we review the interaction of dietary components with the circadian system and illustrate the relationships linking the molecular clock to metabolism and critical roles in the remodeling process.

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Differential effect of fructose on fat metabolism and clock gene expression in hepatocytes vs . myotubes

Cited by 7 publications

References 21 publications

DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1

DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1

Potential Crosstalk between Fructose and Melatonin: A New Role of Melatonin—Inhibiting the Metabolic Effects of Fructose

Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming

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