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Article ; Online: Response to Comment on Jakubowicz et al. 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 2019;42:2171-2180.

Froy, Oren

2019 Volume 43, Issue 1, Page(s) e13–e14

MeSH term(s)	Blood Glucose ; Circadian Clocks ; Diabetes Mellitus, Type 2 ; Diet ; Glycated Hemoglobin A ; Humans ; Insulin ; Up-Regulation
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; Insulin
Language	English
Publishing date	2019-12-17
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dci19-0061
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 365: Show issues

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Article ; Online: β-Hydroxy-β-methylbutyrate (HMB) leads to phospholipase D2 (PLD2) activation and alters circadian rhythms in myotubes.

Cohen-Or, Meytal / Chapnik, Nava / Froy, Oren

Food & function

2024 Volume 15, Issue 8, Page(s) 4389–4398

Abstract: β-Hydroxy-β-methylbutyrate (HMB) is a breakdown product of leucine, which promotes muscle growth. Although some studies indicate that HMB activates AKT and mTOR, others show activation of the downstream effectors, P70S6K and S6, independent of mTOR. Our ... ...

Abstract	β-Hydroxy-β-methylbutyrate (HMB) is a breakdown product of leucine, which promotes muscle growth. Although some studies indicate that HMB activates AKT and mTOR, others show activation of the downstream effectors, P70S6K and S6, independent of mTOR. Our aim was to study the metabolic effect of HMB around the circadian clock in order to determine more accurately the signaling pathway involved. C2C12 myotubes were treated with HMB and clock, metabolic and myogenic markers were measured around the clock. HMB-treated C2C12 myotubes showed no activation of AKT and mTOR, but did show activation of P70S6K and S6. Activation of P70S6K and S6 was also found when myotubes were treated with HMB combined with metformin, an indirect mTOR inhibitor, or rapamycin, a direct mTOR inhibitor. The activation of the P70S6K and S6 independent of AKT and mTOR, was accompanied by increased activation of phospholipase D2 (PLD). In addition, HMB led to high amplitude and advanced circadian rhythms. In conclusion, HMB induces myogenesis in C2C12 by activating P70S6K and S6
MeSH term(s)	Valerates/pharmacology ; Animals ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Mice ; Phospholipase D/metabolism ; Circadian Rhythm/drug effects ; Cell Line ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Muscle Development/drug effects
Chemical Substances	Valerates ; beta-hydroxyisovaleric acid (3F752311CD) ; Phospholipase D (EC 3.1.4.4) ; phospholipase D2 (EC 3.1.4.-) ; Ribosomal Protein S6 Kinases, 70-kDa (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2024-04-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d3fo04174c
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Article: Differential Effect of Fructose in the Presence or Absence of Fatty Acids on Circadian Metabolism in Hepatocytes.

Tsameret, Shani / Chapnik, Nava / Froy, Oren

Metabolites

2023 Volume 13, Issue 2

Abstract: We aimed to explore whether fructose in the absence or presence of fatty acids modulates circadian metabolism in AML-12 hepatocytes. Fructose treatment under steatosis conditions (FruFA) led to fat synthesis resulting in increased triglycerides and ... ...

Abstract	We aimed to explore whether fructose in the absence or presence of fatty acids modulates circadian metabolism in AML-12 hepatocytes. Fructose treatment under steatosis conditions (FruFA) led to fat synthesis resulting in increased triglycerides and cholesterol content. Fructose led to reduced activity of the AMPK and mTOR-signaling pathway. However, FruFA treatment led to inhibition of the AMPK signaling pathway but activation of the mTOR pathway. Fructose also increased the expression of inflammatory markers, whereas the addition of fatty acids dampened their circadian expression. At the clock level, fructose or FruFA altered the expression of the core clock. More specifically, fructose led to altered expression of the BMAL1-RORα-REV-ERBα axis, together with reduced phosphorylated BMAL1 levels. In conclusion, our results show that hepatocytes treated with fructose respond differently if fatty acids are present, leading to a differential effect on metabolism and circadian rhythms. This is achieved by modulating BMAL1 activity and expression.
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13020138
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Article ; Online: Effect of early vs. late time-restricted high-fat feeding on circadian metabolism and weight loss in obese mice.

Tsameret, Shani / Chapnik, Nava / Froy, Oren

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 7, Page(s) 180

Abstract: Time-restricted feeding (TRF) limits the time and duration of food availability without calorie reduction. Although a high-fat (HF) diet leads to disrupted circadian rhythms, TRF can prevent metabolic diseases, emphasizing the importance of the timing ... ...

Abstract	Time-restricted feeding (TRF) limits the time and duration of food availability without calorie reduction. Although a high-fat (HF) diet leads to disrupted circadian rhythms, TRF can prevent metabolic diseases, emphasizing the importance of the timing component. However, the question of when to implement the feeding window and its metabolic effect remains unclear, specifically in obese and metabolically impaired animals. Our aim was to study the effect of early vs. late TRF-HF on diet-induced obese mice in an 8:16 light-dark cycle. C57BL male mice were fed ad libitum a high-fat diet for 14 weeks after which they were given the same food during the early (E-TRF-HF) or late (L-TRF-HF) 8 h of the dark phase for 5 weeks. The control groups were fed ad libitum either a high-fat (AL-HF) or a low-fat diet (AL-LF). Respiratory exchange ratio (RER) was highest for the AL-LF group and the lowest for the AL-HF group. E-TRF-HF led to lower body weight and fat depots, lower glucose, C-peptide, insulin, cholesterol, leptin, TNFα, and ALT levels compared with L-TRF-HF- and AL-HF-fed mice. TRF-HF regardless whether it was early or late led to reduced inflammation and fat accumulation compared with AL-HF-fed mice. E-TRF-HF led to advanced liver circadian rhythms with higher amplitudes and daily expression levels of clock proteins. In addition, TRF-HF led to improved metabolic state in muscle and adipose tissue. In summary, E-TRF-HF leads to increased insulin sensitivity and fat oxidation and decreased body weight, fat profile and inflammation contrary to AL-HF-fed, but comparable to AL-LF-fed mice. These results emphasize the importance of timed feeding compared to ad libitum feeding, specifically to the early hours of the activity period.
MeSH term(s)	Male ; Mice ; Animals ; Mice, Obese ; Mice, Inbred C57BL ; Obesity/metabolism ; Adipose Tissue/metabolism ; Diet, High-Fat/adverse effects ; Inflammation ; Insulin ; Circadian Rhythm/physiology ; Weight Loss
Chemical Substances	Insulin
Language	English
Publishing date	2023-06-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-04834-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 195: Show issues

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Article ; Online: Mucosal Genes Encoding Clock, Inflammation and Their Mutual Regulators Are Disrupted in Pediatric Patients with Active Ulcerative Colitis.

Labes, Sapir / Froy, Oren / Tabach, Yuval / Shamir, Raanan / Shouval, Dror S / Weintraub, Yael

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory ... ...

Abstract	Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory genes in treatment-naïve pediatric patients with UC. Using the Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) platform and R algorithms, we analyzed rectal biopsy transcriptomic data from two cohorts (206 patients with UC vs. 20 healthy controls from the GSE-109142 study, and 43 patients with UC vs. 55 healthy controls from the GSE-117993 study). We compared gene expression levels and correlation of clock genes (
MeSH term(s)	Child ; Humans ; ARNTL Transcription Factors/genetics ; Circadian Rhythm/physiology ; Colitis, Ulcerative/genetics ; Inflammation/genetics ; Interleukin-10 ; Interleukin-6 ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha ; PPAR gamma ; Tumor Necrosis Factor-alpha ; CLOCK Proteins/genetics ; CLOCK Proteins/metabolism ; Period Circadian Proteins/genetics ; Period Circadian Proteins/metabolism ; Cryptochromes/genetics ; Cryptochromes/metabolism
Chemical Substances	ARNTL Transcription Factors ; Interleukin-10 (130068-27-8) ; Interleukin-6 ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha ; PPAR gamma ; Tumor Necrosis Factor-alpha ; CLOCK Proteins (EC 2.3.1.48) ; PER1 protein, human ; Period Circadian Proteins ; PER2 protein, human ; CRY1 protein, human ; Cryptochromes ; CRY2 protein, human
Language	English
Publishing date	2024-01-25
Publishing country	Switzerland
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031488
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Article ; Online: Resveratrol Induces the Fasting State and Alters Circadian Metabolism in Hepatocytes.

Chatam, Opal / Chapnik, Nava / Froy, Oren

Plant foods for human nutrition (Dordrecht, Netherlands)

2022 Volume 77, Issue 1, Page(s) 128–134

Abstract: Resveratrol is a nutritional substance that has both metabolic and circadian effects. While some studies indicate a correlation between resveratrol and reduced gluconeogenesis, others propose the opposite. Our aim was to study the metabolic effect of ... ...

Abstract	Resveratrol is a nutritional substance that has both metabolic and circadian effects. While some studies indicate a correlation between resveratrol and reduced gluconeogenesis, others propose the opposite. Our aim was to study the metabolic effect of resveratrol around the circadian clock in order to determine more accurately the hepatic signaling pathways involved. AML-12 hepatocytes were treated with resveratrol and clock and metabolic markers were measured around the clock. Resveratrol-treated AML-12 hepatocytes showed reduced ratio of the following key metabolic factors: phosphorylated PP2A to total PP2A (pPP2A/PP2A), pAKT/AKT, pFOXO1/FOXO1 and pAMPK/AMPK, indicating inhibition of AKT and AMPK, but activation of PP2A and FOXO1. In addition, the levels of phosphorylated mTOR were low after resveratrol treatment. The levels of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were significantly higher after resveratrol treatment. In accordance with the reduced mTOR activity, the ratio of pBMAL1/BMAL1, the clock transcription factor, also decreased. Bmal1 mRNA oscillated robustly in AML-12 hepatocytes, but resveratrol treatment led to a phase advance and a decrease in its amplitude, similarly to the effect on Srebp1c and Pgc1α mRNA. After resveratrol treatment, daily mRNA levels of Bmal1, Sirt1 and Srebp1c were significantly higher. Resveratrol changes the circadian expression of metabolic and clock genes activating the fasting state and inducing the PP2A-FOXO1-PEPCK pathway.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; AMP-Activated Protein Kinases/pharmacology ; ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; ARNTL Transcription Factors/pharmacology ; Fasting ; Hepatocytes/metabolism ; Humans ; Leukemia, Myeloid, Acute/metabolism ; Liver ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-akt/pharmacology ; RNA, Messenger ; Resveratrol/metabolism ; Resveratrol/pharmacology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; TOR Serine-Threonine Kinases/pharmacology
Chemical Substances	ARNTL Transcription Factors ; RNA, Messenger ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2022-02-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	188869-9
ISSN	1573-9104 ; 0377-3205
ISSN (online)	1573-9104
ISSN	0377-3205
DOI	10.1007/s11130-022-00954-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 967: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A CRY for help to fight fat.

Froy, Oren

American journal of physiology. Endocrinology and metabolism

2013 Volume 304, Issue 11, Page(s) E1129–30

MeSH term(s)	Adipose Tissue, White/metabolism ; Animals ; Circadian Rhythm/physiology ; Cryptochromes/physiology ; Hyperinsulinism/metabolism ; Insulin Resistance/physiology ; Male
Chemical Substances	Cryptochromes
Language	English
Publishing date	2013-06-01
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00233.2013
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Uc I Zs.89: Show issues

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Article ; Online: Circadian aspects of energy metabolism and aging.

Froy, Oren

Ageing research reviews

2013 Volume 12, Issue 4, Page(s) 931–940

Abstract: Life span extension has been a goal of research for several decades. Resetting circadian rhythms leads to well being and increased life span, while clock disruption is associated with increased morbidity accelerated aging. Increased longevity and ... ...

Abstract	Life span extension has been a goal of research for several decades. Resetting circadian rhythms leads to well being and increased life span, while clock disruption is associated with increased morbidity accelerated aging. Increased longevity and improved health can be achieved by different feeding regimens that reset circadian rhythms and may lead to better synchrony in metabolism and physiology. This review focuses on the circadian aspects of energy metabolism and their relationship with aging in mammals.
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Animals ; CLOCK Proteins/biosynthesis ; CLOCK Proteins/genetics ; Caloric Restriction/methods ; Circadian Rhythm/physiology ; Energy Metabolism/physiology ; Humans ; Suprachiasmatic Nucleus/metabolism
Chemical Substances	CLOCK Proteins (EC 2.3.1.48)
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2013.09.002
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Zs.A 5579: Show issues

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Article ; Online: Erratum to Relationship among chrononutrition, sleep, and glycemic control in women with gestational diabetes mellitus: a randomized controlled trial. American Journal of Obstetrics & Gynecology MFM. Volume 4, Issue 5, September 2022, 100660.

Messika, Amalia / Toledano, Yoel / Hadar, Eran / Shmuel, Eliassaf / Tauman, Riva / Shamir, Raanan / Froy, Oren

American journal of obstetrics & gynecology MFM

2022 Volume 4, Issue 6, Page(s) 100701

Language	English
Publishing date	2022-08-23
Publishing country	United States
Document type	Published Erratum
ISSN	2589-9333
ISSN (online)	2589-9333
DOI	10.1016/j.ajogmf.2022.100701
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Article: Resveratrol Induces the Fasting State and Alters Circadian Metabolism in Hepatocytes

Chatam, Opal / Chapnik, Nava / Froy, Oren

Plant foods for human nutrition. 2022 Mar., v. 77, no. 1

2022

Abstract	Resveratrol is a nutritional substance that has both metabolic and circadian effects. While some studies indicate a correlation between resveratrol and reduced gluconeogenesis, others propose the opposite. Our aim was to study the metabolic effect of resveratrol around the circadian clock in order to determine more accurately the hepatic signaling pathways involved. AML-12 hepatocytes were treated with resveratrol and clock and metabolic markers were measured around the clock. Resveratrol-treated AML-12 hepatocytes showed reduced ratio of the following key metabolic factors: phosphorylated PP2A to total PP2A (pPP2A/PP2A), pAKT/AKT, pFOXO1/FOXO1 and pAMPK/AMPK, indicating inhibition of AKT and AMPK, but activation of PP2A and FOXO1. In addition, the levels of phosphorylated mTOR were low after resveratrol treatment. The levels of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were significantly higher after resveratrol treatment. In accordance with the reduced mTOR activity, the ratio of pBMAL1/BMAL1, the clock transcription factor, also decreased. Bmal1 mRNA oscillated robustly in AML-12 hepatocytes, but resveratrol treatment led to a phase advance and a decrease in its amplitude, similarly to the effect on Srebp1c and Pgc1α mRNA. After resveratrol treatment, daily mRNA levels of Bmal1, Sirt1 and Srebp1c were significantly higher. Resveratrol changes the circadian expression of metabolic and clock genes activating the fasting state and inducing the PP2A-FOXO1-PEPCK pathway.
Keywords	carboxy-lyases ; circadian clocks ; gluconeogenesis ; hepatocytes ; human nutrition ; resveratrol ; transcription factors
Language	English
Dates of publication	2022-03
Size	p. 128-134.
Publishing place	Springer US
Document type	Article
ZDB-ID	221100-2
ISSN	1573-9104 ; 0921-9668
ISSN (online)	1573-9104
ISSN	0921-9668
DOI	10.1007/s11130-022-00954-7
Database	NAL-Catalogue (AGRICOLA)

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Z 2814: Show issues

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