Effect of metformin and lipid emulsion on the circadian gene expression in muscle cells

Barnea, Maayan; Cohen-Yogev, Tamar; Chapnik, Nava; Madar, Zecharia; Froy, Oren

doi:10.1016/j.biocel.2014.05.014

Cited by 10 publications

(6 citation statements)

References 58 publications

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“…Previous studies demonstrated that metformin activates adenosine monophosphate-activated protein kinase (AMPK) and inhibits glucose phosphorylation and glycolysis through an AMPK-independent pathway ( 32, 33 ). In addition, metformin has been shown to serve as a clock regulator and rebuilds the circadian clock via the activation of AMPK ( 34–36 ). In this study, we treated TR cells with metformin to detect the expression of AMPK and PER1 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In our study, metformin not only inhibited HK2 but also induced the degradation of PER1 protein in cells and mice. Previous reports have demonstrated that metformin acts as a clock regulator and rebuilds the clock, depending on the activation of AMPK ( 34–36 ). For instance, metformin treatment caused AMPK activation and mPer1/2 degradation in mouse fibroblasts and shortened the phase of the circadian cycle.…”

Section: Discussionmentioning

confidence: 99%

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Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer

Wang

Huang

et al. 2022

Cancer Research

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Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC), but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) GC cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern (higher at zeitgeber time 6, lower at zeitgeber time 18). Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of peroxisome proliferator-activated receptor γ (PPARγ) and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at zeitgeber time 6 significantly improved trastuzumab efficacy in GC. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in GC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer

Wang

Huang

et al. 2022

Cancer Research

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“…Cells were homogenized in lysis buffer, as previously described . Samples were run on a 12% sodium dodecyl sulfate (SDS) polyacrylamide gel and transferred onto nitrocellulose membranes.…”

Section: Methodsmentioning

confidence: 99%

Serotonin Prevents Differentiation of Brown Adipocytes by Interfering with Their Clock

Rozenblit-Susan

Chapnik

Froy

2019

Obesity

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Objective Serotonin was shown to interfere with the differentiation of brown adipocytes. In addition, clock components inhibit brown adipogenesis through direct transcriptional control of key components of the transforming growth factor β pathway. The aim of this study was to investigate whether serotonin abrogates brown adipogenesis by affecting clock functionality. Methods Nondifferentiated and differentiated HIB1B brown adipocytes were treated with serotonin, and their clock expression and functionality and differentiation state were examined. Results Nondifferentiated HIB1B brown adipocytes treated with serotonin showed increased brown adipocyte markers alongside increased brain‐muscle Arnt‐like protein 1 (Bmal1) and RAR related orphan receptor A (Rora) but decreased nuclear receptor Rev‐erbα mRNA levels. BMAL1 overexpression together with serotonin led to significantly lower brown adipocyte markers. Serotonin in the differentiation cocktail led to reduced brown adipocyte markers as well as clock gene expression. After differentiation, serotonin treatment significantly decreased brown adipocyte markers and reduced BMAL1 and RORα but increased REV‐ERBα protein levels. Addition of serotonin to the differentiation medium or addition after differentiation reduced activity of calcium/calmodulin‐dependent protein kinase type II subunit gamma, which interferes with circadian locomoter output cycles protein kaput (CLOCK):BMAL1 dimerization and transactivation. Conclusions Clock expression is required at the early stages of differentiation to brown adipocytes, and serotonin interferes with this process by modulating clock functionality. Serotonin interferes with clock functionality by reducing the levels of the active form of calcium/calmodulin‐dependent protein kinase type II subunit gamma.

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“…Hansen et al (21) reported rhythmic expression in the same genes, but Per1 and Cry2 could not be detected, after serum shock synchronization. In differentiated myotubes of C2C12s, a mouse skeletal-muscle cell line, the expression of Clock, Bmal1, Cry1, Per1, and Per2 was found to be rhythmic after dexamethasone synchronization (22). This direct juxtaposition of available data on the skeletal-muscle clocks in mice and humans reveals that if expression is normalized to activity/rest cycles, the skeletal-muscle clocks of humans and mice show very common patterns of gene expression, as illustrated in Figures 2A-2B.…”

Section: The Skeletal-muscle Clocks In Rodents and Humansmentioning

confidence: 99%

Ticking for Metabolic Health: The Skeletal‐Muscle Clocks

Gutierrez‐Monreal

Harmsen

Schrauwen

et al. 2020

Obesity

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Effect of metformin and lipid emulsion on the circadian gene expression in muscle cells

Cited by 10 publications

References 58 publications

Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer

Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer

Serotonin Prevents Differentiation of Brown Adipocytes by Interfering with Their Clock

Ticking for Metabolic Health: The Skeletal‐Muscle Clocks

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