ArticleThe Journal of clinical investigation2020
Nonalcoholic fatty liver disease in CLOCK mutant mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Redox rhythms promote fitness by modulating ageing-dependent reprogramming.Nature metabolism · 2026Article
- Cysteine 129 in Pla2g12b Is Critical for Intestinal and Hepatic Lipoprotein Secretion in Mice.Cellular and molecular gastroenterology and hepatology · 2026Article
- The importance of sex dimorphism in liver metabolism and progressive liver diseases.Biology of sex differences · 2025Review
- Chrysanthemum morifolium extract improves metabolic dysfunction-associated fatty liver disease by regulating lipid metabolism.Scientific reports · 2025Article
- Article
- Rev‑erbα: The circadian guardian against NLRP3‑driven liver fibrosis.Molecular medicine reports · 2025Article
- Knockdown of the Clock gene in the liver aggravates MASLD in mice via inhibiting lipophagy.Molecular and cellular biochemistry · 2025Article
- Review
- Circadian Deregulation: Back Facing the Sun Toward Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development.Nutrients · 2024Review
- Circadian Regulation of Lipid Metabolism during Pregnancy.International journal of molecular sciences · 2024Review
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- Neuroprotection via Carbon Monoxide Depends on the Circadian Regulation of CD36-Mediated Microglial Erythrophagocytosis in Hemorrhagic Stroke.International journal of molecular sciences · 2024Article
- Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology.Nature reviews. Gastroenterology & hepatology · 2023Review
- Reciprocal regulation between the molecular clock and kidney injury.Life science alliance · 2023Article
- Circadian rhythms and inflammatory diseases of the liver and gut.Liver research (Beijing, China) · 2023Review
- Liver-SpecificNutrients · 2023Article
- Genetic and Diet-Induced Animal Models for Non-Alcoholic Fatty Liver Disease (NAFLD) Research.International journal of molecular sciences · 2022Review
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Bmal1 regulates production of larger lipoproteins by modulating cAMP-responsive element-binding protein H and apolipoprotein AIV.Hepatology (Baltimore, Md.) · 2022Article
- Chronic constant light exposure aggravates high fat diet-induced renal injury in rats.Frontiers in endocrinology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming a major health issue as obesity increases around the world. We studied the effect of a circadian locomotor output cycles kaput (CLOCK) mutant (ClkΔ19/Δ19) protein on hepatic lipid metabolism in C57BL/6 Clkwt/wt and apolipoprotein E-deficient (Apoe-/-) mice. Both ClkΔ19/Δ19 and ClkΔ19/Δ19 Apoe-/- mice developed a full spectrum of liver diseases (steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma) recognized in human NAFLD when challenged with a Western diet, lipopolysaccharide, or CoCl2. We identified induction of CD36 and hypoxia-inducible factor 1α (HIF1α) proteins as contributing factors for NAFLD. Mechanistic studies showed that WT CLOCK protein interacted with the E-box enhancer elements in the promoters of the proline hydroxylase domain (PHD) proteins to increase expression. In ClkΔ19/Δ19 mice, PHD levels were low, and HIF1α protein levels were increased. When its levels were high, HIF1α interacted with the Cd36 promoter to augment expression and enhance fatty acid uptake. Thus, these studies establish a regulatory link among circadian rhythms, hypoxia response, fatty acid uptake, and NAFLD. The mouse models described here may be useful for further mechanistic studies in the progression of liver diseases and in the discovery of drugs for the treatment of these disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.