Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding

Yu, Fangjun; Wang, Zhigang; Zhang, Tianpeng; Chen, Xun; Xu, Haiman; Wang, Fei; Guo, Lianxia; Chen, Min; Liu, Kaisheng; Wu, Baojian

doi:10.1038/s41467-021-25674-5

Cited by 60 publications

(33 citation statements)

References 55 publications

(81 reference statements)

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“…Circulating total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol concentrations were significantly higher under the Puri-starch regimen compared with Chow during the whole course of the experiment ( Figures 2G–I ). Similar cholesterol levels were observed before in several studies that applied the Puri-starch diet as control condition ( 19 , 23 – 25 ). Moreover, alanine transaminase (ALT) and aspartate transaminase (AST) were increased after 30 or after 20 and 30 weeks, respectively ( Figures 2M,N ), indicating hepatocyte injury.…”

Section: Resultssupporting

confidence: 87%

Starch and Fiber Contents of Purified Control Diets Differentially Affect Hepatic Lipid Homeostasis and Gut Microbiota Composition

et al. 2022

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BackgroundInterpretation of results from diet-induced-obesity (DIO) studies critically depends on control conditions. Grain-based chows are optimized for rodent nutrition but do not match the defined composition of purified diets used for DIO, severely limiting the comparability. Purified control diets are recommended but often contain high starch and only minor fiber amounts. It is unknown whether this composition leads to metabolic alterations compared with chow and whether the addition of refined fibers at the expense of starch affects these changes.MethodsIn this experiment, 6-week-old C57BL/6N mice were fed (i) a conventional purified control diet (high-starch, low-fiber; Puri-starch), (ii) an alternative, custom-made purified control diet containing pectin and inulin (medium-starch, higher-fiber; Puri-fiber), or (iii) grain-based chow for 30 weeks (N = 8–10).ResultsPuri-starch feeding resulted in significantly elevated levels of plasma insulin (p = 0.004), cholesterol (p < 0.001), and transaminases (AST p = 0.002, ALT p = 0.001), hepatic de novo lipogenesis and liver steatosis, and an altered gut microbiota composition compared with chow-fed mice. In contrast, Puri-fiber exerted only minor effects on systemic parameters and liver lipid homeostasis, and promoted a distinct gut microbiota composition.ConclusionCarbohydrate-rich purified diets trigger a metabolic status possibly masking pathological effects of nutrients under study, restricting its use as control condition. The addition of refined fibers is suited to create purified, yet physiological control diets for DIO research.

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Section: Resultssupporting

confidence: 87%

Starch and Fiber Contents of Purified Control Diets Differentially Affect Hepatic Lipid Homeostasis and Gut Microbiota Composition

et al. 2022

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“…This result suggests that while a high amplitude circadian clock is key to protect against the development of numerous diseases and pathologies, a fully functional BMAL1 can also have detrimental effects. In support of this concept, Bmal1 deficiency in the intestine protects against HFD obesity ( 61 ), while its deletion in macrophages improves defense against bacterial infection ( 62 ). Moreover, Bmal1 deletion in myeloid cells attenuates the development of atherosclerosis ( 63 ).…”

Section: Discussionmentioning

confidence: 95%

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease

Jouffe

Weger

Martín

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance While increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.

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“…Recent studies revealed that circadian desynchrony was closely related to the disruption of glucose and lipid homeostasis [ 32 , 33 , 34 , 35 , 36 ]. According to Li et al, the misalignment of circadian clock genes could be caused in the lipid accumulation model using HepG2 cells [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells

Zhang

2022

IJMS

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Metabolic disorders are closely associated with the dysregulation of circadian rhythms. Many bioactive components with lipid metabolism-regulating effects have been reported to function through circadian clock-related mechanisms. As the main pungent principle of black pepper, piperine (PIP) has been demonstrated to possess anti-obesity bioactivity by affecting hepatic lipid metabolism-related factors. However, whether the circadian clock genes Bmal1 and Clock are involved in the protective effect of PIP against lipid metabolism disorders remains unknown. In this work, oleic acid (OA) induced lipid accumulation in HepG2 cells. The effect of PIP on redox status, mitochondrial functions, and circadian rhythms of core clock genes were evaluated. Results revealed that PIP alleviated circadian desynchrony, ROS overproduction, and mitochondrial dysfunction. A mechanism study showed that PIP could activate the SREBP-1c/PPARγ and AMPK/AKT-mTOR signaling pathways in a Bmal1/Clock-dependent manner in HepG2 cells. These results indicated that Bmal1 and Clock played important roles in the regulating effect of PIP on hepatic lipid homeostasis.

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Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding

Cited by 60 publications

References 55 publications

Starch and Fiber Contents of Purified Control Diets Differentially Affect Hepatic Lipid Homeostasis and Gut Microbiota Composition

Starch and Fiber Contents of Purified Control Diets Differentially Affect Hepatic Lipid Homeostasis and Gut Microbiota Composition

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells

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