Journal article
Gastric bypass alters diurnal feeding behavior and reprograms hepatic clock to regulate endogenous glucose flux
JCI insight, Vol.8(6), e166618
03/22/2023
DOI: 10.1172/jci.insight.166618
PMCID: PMC10070113
PMID: 36787197
Abstract
The molecular clock machinery regulates several homeostatic rhythms, including glucose metabolism. We previously demonstrated that Roux-en Y Gastric Bypass (RYGB) has a weight-independent effect on glucose homeostasis, and transiently reduces food intake. In this study we investigate the effects of RYGB on diurnal eating behavior as well as its effects on the molecular clock, and its requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reverses the high fat diet-induced disruption in diurnal eating pattern during the early post-surgery phase of food reduction. "Dark-cycle" pair-feeding experiments improved glucose tolerance to the level of bypass-operated animals during the physiologic "fasting" phase (Zeitgeber ZT2), but not the "feeding" phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induces a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus (SCN). In addition, we show that weight loss effects are attenuated in obese ClockΔ19 mutant mice post-RYGB that also fail to improve glucose metabolism after surgery, specifically hepatic glucose production. We conclude that RYGB reprograms the peripheral clock within the liver early after surgery to alter diurnal eating behavior and regulate hepatic glucose flux.
Details
- Title: Subtitle
- Gastric bypass alters diurnal feeding behavior and reprograms hepatic clock to regulate endogenous glucose flux
- Creators
- Yuanchao Ye - University of IowaMarwa Abu El Haija - Stanford University School of MedicineReine Obeid - American University of BeirutHussein Herz - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, United States of AmericaLiping Tian - Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaBenjamin Linden - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, United States of AmericaYi Chu - University of IowaDeng Fu Guo - University of IowaDaniel C Levine - Northwestern UniversityJonathan Cedernaes - Northwestern UniversityKamal Rahmouni - University of IowaJoseph Bass - Northwestern UniversityMohamad Mokadem - University of Iowa
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.8(6), e166618
- DOI
- 10.1172/jci.insight.166618
- PMID
- 36787197
- PMCID
- PMC10070113
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- Grant note
- DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: BX004774; DOI: 10.13039/100000738, name: U.S Department of Veterans Affairs, award: BX005173; name: NIH- NIDDK, award: R01DK127800, R01DK113011, R01DK090625, R01DK050203; name: National Institute of Aging, award: R01AG065988, P01AG011412; name: University of Chicago Diabetes Research and Training Center, award: P30DK020595; name: National Institute of Health, award: K99DK124682.
- Language
- English
- Electronic publication date
- 02/14/2023
- Date published
- 03/22/2023
- Academic Unit
- Gastroenterology and Hepatology; Iowa Neuroscience Institute; Surgery; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984366459602771
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