Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light–12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.

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The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats

Life Sciences ◽

10.1016/s0024-3205(99)00210-6 ◽

1999 ◽

Vol 64 (26) ◽

pp. 2523-2534 ◽

Cited By ~ 61

Author(s):

Simone van den Heiligenberg ◽

Petra Deprés-Brummer ◽

Hervé Barbason ◽

Bruno Claustrat ◽

Michel Reynes ◽

...

Keyword(s):

Light Exposure ◽

Constant Light ◽

Promoting Effect

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The Impact of Incretin-Based Medications on Lipid Metabolism

Journal of Diabetes Research ◽

10.1155/2021/1815178 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Habib Yaribeygi ◽

Mina Maleki ◽

Alexandra E. Butler ◽

Tannaz Jamialahmadi ◽

Amirhossein Sahebkar

Keyword(s):

Lipid Metabolism ◽

Diabetes Complications ◽

Clinical Evidence ◽

Lipid Homeostasis ◽

Beneficial Effects ◽

Chronic Hyperglycemia ◽

Current Review ◽

Patients With Diabetes ◽

Cellular Pathways ◽

The Impact

Pathophysiological pathways that are induced by chronic hyperglycemia negatively impact lipid metabolism. Thus, diabetes is commonly accompanied by varying degrees of dyslipidemia which is itself a major risk factor for further macro- and microvascular diabetes complications such as atherosclerosis and nephropathy. Therefore, normalizing lipid metabolism is an attractive goal for therapy in patients with diabetes. Incretin-based medications are a novel group of antidiabetic agents with potent hypoglycemic effects. While the impact of incretins on glucose metabolism is clear, recent evidence indicates their positive modulatory roles on various aspects of lipid metabolism. Therefore, incretins may offer additional beneficial effects beyond that of glucose normalization. In the current review, how these antidiabetic medications can regulate lipid homeostasis and the possible cellular pathways involved are discussed, incorporating related clinical evidence about incretin effects on lipid homeostasis.

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Comparative Effects of Native and Defatted Flaxseeds on Intestinal Enzyme Activity and Lipid Metabolism in Rats Fed a High-Fat Diet Containing Cholic Acid

Nutrients ◽

10.3390/nu10091181 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1181 ◽

Cited By ~ 8

Author(s):

Paulina Opyd ◽

Adam Jurgoński ◽

Jerzy Juśkiewicz ◽

Bartosz Fotschki ◽

Jarosław Koza

Keyword(s):

Lipid Metabolism ◽

Cholic Acid ◽

Lipid Absorption ◽

Cholesterol Concentration ◽

Control Group ◽

Standard Diet ◽

High Fat ◽

Hepatic Expression ◽

Beneficial Effects ◽

Triglyceride Accumulation

We hypothesize that defatting is an important factor that can determine the beneficial effects of flaxseeds on rats with diet-induced disorders. The experiment lasts 8 weeks and is conducted on Wistar rats allocated to four groups as follows: a control group fed with a standard diet; a high-fat (HF) group fed with a diet containing 21% fat and 0.1% cholic acid as a stimulator of lipid absorption; an HF group fed a diet supplemented with 1% native flaxseeds; and an HF group fed a diet supplemented with 1% defatted flaxseeds. In the HF group, several unfavourable changes in the gut and lipid metabolism are observed. Supplementation of the HF diet with native flaxseeds prevent an increase in colonic β-glucuronidase activity, whereas dietary defatted flaxseeds increase mucosal disaccharidase activities in the small intestine (sucrose, maltase and lactase). Regardless of the form of supplementation, dietary flaxseeds increase bacterial glycolytic activity in the distal intestine and decrease hepatic fat, especially triglyceride, accumulation. Both flaxseed forms decrease lipid peroxidation in the kidneys and increase the blood HDL cholesterol concentration with the native form being more efficient in the former and the defatted form being more efficient in the latter. The lipid-modulating effects of defatted flaxseeds are associated with reduced hepatic expression of peroxisome proliferator-activated receptor α, which is not the case in terms of native flaxseeds. Dietary supplementation with a relatively small amount of flaxseeds can exert beneficial effects on gut functions and lipid metabolism in rats, and these effects are affected by defatting to some extent.

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PS2 - 10. Constant light exposure disturbs circadian rhythm in energy metabolism and insulin sensitivity

Nederlands Tijdschrift voor Diabetologie ◽

10.1007/s12467-011-0035-2 ◽

2011 ◽

Vol 9 (3) ◽

pp. 96-97

Author(s):

Claudia P. Coomans ◽

Sjoerd A. A. van den Berg ◽

Thijs Houben ◽

Jan B. van Klinken ◽

Amanda C. M. Pronk ◽

...

Keyword(s):

Circadian Rhythm ◽

Insulin Sensitivity ◽

Energy Metabolism ◽

Light Exposure ◽

Constant Light

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Comparative studies on phospholipase A2 as a marker for the gut microbiota-liver-brain axis in a rodent model of autism.

Current Proteomics ◽

10.2174/1570164617999200519100634 ◽

2020 ◽

Vol 17 ◽

Author(s):

Abeer Al-Dbass ◽

Abir Ben Bacha ◽

Nadine MS Moubayed ◽

Ramesa Shafi Bhat ◽

Manar Al-Mutairi ◽

...

Keyword(s):

Lipid Metabolism ◽

Treatment Group ◽

Vitamin B12 ◽

Phospholipase A2 ◽

Combined Treatment ◽

Lipid Homeostasis ◽

Control Group ◽

Peripheral Tissues ◽

Group I

Background: Lipid homeostasis and gut flora can be related to many metabolic diseases, especially autism. Lipid metabolism in the brain can control neuronal structure and function and can also take part in signal transduction pathways to control metabolism in peripheral tissues, especially in the liver. Impaired phospholipid metabolism promotes oxidative stress and neuroinflammation and is therefore directly related to autism. Objective: The effect of propionic acid (PPA) toxicity on lipid homeostasis in the gut-liver-brain axis was evaluated to understand their inter-connection. Cytosolic phospholipase A2 (cPLA2) concentration and activity was measured in autistic model and protective role of omega-3 (ω-3) and vitamin B12 was evaluated. Methods: Animals were divided into five groups: Group I (control group); Group II (autistic model treated with neurotoxic dose of PPA); Group III (treated with vitamin B12 (16.7 mg/kg/day) for 30 days post PPA treatment); Group IV (treated with ω-3 (200 mg/kg body weight/day) for 30 days post PPA treatment ;Group V (combined dose of ω-3 and Vitamin B12, for 30 days post PPA treatment). Phospholipase A2 activity and protein expression level in the liver homogenate of all the groups was analyzed by western blotting and was compared to brain cPLA2. Results: PPA increased the levels of liver and brain cPLA2. However, independent or combined treatment with ω-3 and vitamin B12 was effective in neutralizing its effect. Moreover, PPA-induced dysbiosis, which was ameliorated with the above treatments. Conclusions: This study showed the role of cPLA2 as a lipid metabolism marker, related to PPA-induced inflammation through a highly interactive gut-liver-brain axis.

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Agomelatine Treatment Corrects Depressive-like Behaviour Induced by Chronic Constant Light Exposure through Modulation of Circadian Rhythm of Corticosterone Release

10.7546/crabs.2019.04.15 ◽

2019 ◽

Author(s):

Jana Tchekalarova ◽

Tsveta Stoyanova ◽

Rumyana Gesheva ◽

Milena Atanasova

Keyword(s):

Circadian Rhythm ◽

Light Exposure ◽

Constant Light ◽

Corticosterone Release

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DYSLIPIDEMIA IN THYROID DISORDERS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i7.1308 ◽

2020 ◽

Vol 4 (7) ◽

Author(s):

Kashish Narula ◽

Narendra Kumar Dara ◽

Shyam Lal Meena

Keyword(s):

Lipid Metabolism ◽

Thyroid Dysfunction ◽

Cross Sectional Study ◽

Control Group ◽

Thyroid Disorders ◽

Cross Sectional ◽

Carbohydrate And Lipid Metabolism ◽

History Of ◽

Thyroid Profile ◽

Basal Energy Expenditure

Background: Thyroid hormones influence nearly all major metabolic pathways. Their most obvious and well-known action is the increase in basal energy expenditure obtained by acting on protein, carbohydrate and lipid metabolism. The lipid metabolism is more influenced by the thyroid hormone. Methods: A cross-sectional study was conducted on 100 patients with suspicion of thyroid disorders were taken as cases. One hundred patients with normal thyroid profile and no history of other chronic diseases were taken as control group. Results: The serum TC, TG and LDL levels in hypothyroid individuals (both overt and subclinical) were significantly higher than euthyroid subjects but the levels were comparable between hyperthyroid and euthyroid group. Conclusion: Dyslipidemias are associated with thyroid disorders, so biochemical screening for thyroid dysfunction in all dyslipidemic patients. Therefore, patients presenting with dyslipidemia are recommended for investigation to explore thyroid dysfunction. Keywords: Thyroid profile, Total cholesterol, Triglycerides and LDL

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Dietary Quercetin Alleviated DSS-induced Colitis in Mice Through Several Possible Pathways by Transcriptome Analysis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200711152726 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1666-1673 ◽

Cited By ~ 1

Author(s):

Yuanyang Dong ◽

Jiaqi Lei ◽

Bingkun Zhang

Keyword(s):

Antioxidant Capacity ◽

Underlying Mechanism ◽

Control Group ◽

Sequencing Analysis ◽

Colon Tissue ◽

Beneficial Effects ◽

Intestinal Integrity ◽

Inflammatory Bowel ◽

Vegetables And Fruits ◽

Key Pathways

Background: The prevalence of inflammatory bowel disease is rapidly increasing around the world. Quercetin is a flavonoid commonly found in vegetables and fruits and has been reported to exert numerous pharmacological activities such as enhancing antioxidant capacity or suppressing inflammation. Objective: We aimed to explore whether quercetin was effective for IBD and the underlying mechanism of quercetin for the ameliorative effects on the DSS-induced colitis in mice. Methods: Thirty-six mice were randomly assigned to three treatments, including the control group (Ctr), DSS-induced colitis group (DSS) and DSS-induced colitis supplemented with 500 ppm quercetin (DQ500). Colitis was induced by DSS intake, and body weight was recorded every day. After six days administration of DSS, intestinal permeability was measured, and the liver was taken for antioxidant enzyme tests. Colonic tissue was taken for the histopathlogical score and RNA-sequencing analysis. Results: In this experiment, dietary quercetin for 500ppm alleviated the DSS-induced colitis, possibly by strengthening intestinal integrity, liver antioxidant capacity. Based on the results of the transcriptome of colon tissue, several key genes were modulated by quercetin. ERK1/2-FKBP pathway and RXR-STAT3 pathway were involved in the development of IBD, furthermore, in the down-regulation of S100a8/9, FBN2 contributed to lowering the risk of colongenesis. Conclusion: We demonstrated that dietary quercetin alleviated the DSS-induced colitis in mice. This is most likely due to its beneficial effects on intestinal integrity and modulation of several key pathways. Based on our research, quercetin was a promising candidate for IBD and its pharmaceutical effects on both IBD and colongenesis need further research.

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