scholarly journals Circadian regulation of lipid metabolism

2016 ◽  
Vol 75 (4) ◽  
pp. 440-450 ◽  
Author(s):  
Joshua J Gooley
Keyword(s):  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Circadian Rhythms ◽  
Metabolic Pathways ◽  
Circadian System ◽  
Lipid Absorption ◽  
Acid Oxidation ◽  
Circadian Regulation ◽  
Peripheral Tissues ◽  
Lipid Species

The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

scholarly journals Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism

2017 ◽  
Vol 312 (1) ◽  
pp. E11-E18 ◽  
Author(s):  
Anantha Metlakunta ◽  
Wan Huang ◽  
Maja Stefanovic-Racic ◽  
Nikolaos Dedousis ◽  
Ian Sipula ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Kupffer Cells ◽  
Liver Lipid ◽  
Myeloid Cell ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Acute Effects ◽  
Peripheral Tissues ◽  
Liver Lipid Metabolism

Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin.

scholarly journals Circadian Clock and The Cardiometabolic Risk

2010 ◽  
Vol 2 (2) ◽  
pp. 16
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Circadian Rhythms ◽  
Cardiometabolic Risk ◽  
Clock Genes ◽  
Epidemiological Data ◽  
Circadian System ◽  
Temporal Organization ◽  
Liver Fat ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Rotation Of The Earth

BACKGROUND: Epidemiological data reveal parallel trends of decreasing sleep duration and increases in metabolic disorders such as obesity, diabetes and hypertension. There is growing evidence that these trends are mechanistically related.CONTENT: The circadian system orchestrates the temporal organization of many aspects of physiology, including metabolism, in synchrony with the 24 hours rotation of the Earth. The circadian system is a complex feedback network that involves interactions between the central nervous system and peripheral tissues. Circadian regulation is intimately linked to metabolic homeostasis and that dysregulation of circadian rhythms can contribute to disease. Conversely, metabolic signals also feed back into the circadian system, modulating circadian gene expression and behavior.SUMMARY: Both inter- and intraorgan desynchrony may be involved in the pathogenesis of cardiometabolic disease attributable to effects in brain and multiple metabolic tissues including heart, liver, fat, muscle, pancreas and gut. Efforts to dissect the molecular mediators that coordinate circadian, metabolic, and cardiovascular systems may ultimately lead to both improved therapeutics and preventive interventions.KEYWORDS: circadian rhythms, clock genes, nuclear receptor, sleep, obesity, cardiometabolic risk

scholarly journals ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism

2018 ◽  
Vol 115 (40) ◽  
pp. E9499-E9506 ◽  
Author(s):  
Zhiguang Huang ◽  
Menglu Zhang ◽  
Abigail A. Plec ◽  
Sandi Jo Estill ◽  
Ling Cai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Therapeutic Benefit ◽  
Dietary Lipid ◽  
Lipid Absorption ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Acetyl Coa Synthesis ◽  
Lipid Transporters

Acetyl-CoA synthetase 2 (ACSS2) is a conserved nucleocytosolic enzyme that converts acetate to acetyl-CoA. Adult mice lacking ACSS2 appear phenotypically normal but exhibit reduced tumor burdens in mouse models of liver cancer. The normal physiological functions of this alternate pathway of acetyl-CoA synthesis remain unclear, however. Here, we reveal that mice lacking ACSS2 exhibit a significant reduction in body weight and hepatic steatosis in a diet-induced obesity model. ACSS2 deficiency reduces dietary lipid absorption by the intestine and also perturbs repartitioning and utilization of triglycerides from adipose tissue to the liver due to lowered expression of lipid transporters and fatty acid oxidation genes. In this manner, ACSS2 promotes the systemic storage or metabolism of fat according to the fed or fasted state through the selective regulation of genes involved in lipid metabolism. Thus, targeting ACSS2 may offer a therapeutic benefit for the treatment of fatty liver disease.

Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome

2008 ◽  
Vol 114 (3) ◽  
pp. 183-193 ◽  
Author(s):  
Concepción M. Aguilera ◽  
Mercedes Gil-Campos ◽  
Ramón Cañete ◽  
Ángel Gil
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Oxidation ◽  
Plasma Lipids ◽  
Density Lipoprotein ◽  
Cellular Fatty Acid ◽  
Acid Oxidation ◽  
Subsequent Increase ◽  
Peripheral Tissues

The MS (metabolic syndrome) is a cluster of clinical and biochemical abnormalities characterized by central obesity, dyslipidaemia [hypertriglyceridaemia and decreased HDL-C (high-density lipoprotein cholesterol)], glucose intolerance and hypertension. Insulin resistance, hyperleptinaemia and low plasma levels of adiponectin are also widely related to features of the MS. This review focuses on lipid metabolism alterations associated with the MS, paying special attention to changes in plasma lipids and cellular fatty acid oxidation. Lipid metabolism alterations in liver and peripheral tissues are addressed, with particular reference to adipose and muscle tissues, and the mechanisms by which some adipokines, namely leptin and adiponectin, mediate the regulation of fatty acid oxidation in those tissues. Activation of the AMPK (AMP-dependent kinase) pathway, together with a subsequent increase in fatty acid oxidation, appear to constitute the main mechanism of action of these hormones in the regulation of lipid metabolism. Decreased activation of AMPK appears to have a role in the development of features of the MS. In addition, alteration of AMPK signalling in the hypothalamus, which may function as a sensor of nutrient availability, integrating multiple nutritional and hormonal signals, may have a key role in the appearance of the MS.

scholarly journals Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXR-Regulated and CLOCK/BMAL1-Regulated Systems

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Koh-ichi Nakamura ◽  
Ikuo Inoue ◽  
Seiichiro Takahashi ◽  
Tsugikazu Komoda ◽  
Shigehiro Katayama
Keyword(s):  
Transcriptional Regulation ◽  
Lipid Metabolism ◽  
Transcriptional Activity ◽  
Circadian System ◽  
Retinol Binding Protein ◽  
Lipid Absorption ◽  
Response Elements ◽  
Clock System ◽  
Acyl Coa Oxidase ◽  
Cellular Retinol Binding Protein

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXR was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPAR/RXR. These results suggest that there may be crosstalk between the PPARs/RXR-regulated system and the CLOCK/BMAL1-regulated system.

The Gut–Liver Axis in the Control of Energy Metabolism and Food Intake in Animals

2020 ◽  
Vol 8 (1) ◽  
pp. 295-319 ◽  
Author(s):  
Robert Ringseis ◽  
Denise K. Gessner ◽  
Klaus Eder
Keyword(s):  
Energy Metabolism ◽  
Food Intake ◽  
Gut Microbiota ◽  
Metabolic Pathways ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Peripheral Tissues ◽  
Communication Signals ◽  
Microbial Dysbiosis ◽  
Hypothalamic Inflammation

Recent research has convincingly demonstrated a bidirectional communication axis between the gut and liver that enables the gut microbiota to strongly affect animals’ feeding behavior and energy metabolism. As such, the gut–liver axis enables the host to control and shape the gut microbiota and to protect the intestinal barrier. Gut microbiota–host communication is based on several gut-derived compounds, such as short-chain fatty acids, bile acids, methylamines, amino acid–derived metabolites, and microbial-associated molecular patterns, which act as communication signals, and multiple host receptors, which sense the signals, thereby stimulating signaling and metabolic pathways in all key tissues of energy metabolism and food intake regulation. Disturbance in the microbial ecosystem balance, or microbial dysbiosis, causes profound derangements in the regulation of appetite and satiety in the hypothalamic centers of the brain and in key metabolic pathways in peripheral tissues owing to intestinal barrier disruption and subsequent induction of hepatic and hypothalamic inflammation.

scholarly journals Post-Translational Mechanisms of Plant Circadian Regulation

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 325
Author(s):  
Jiapei Yan ◽  
Yeon Jeong Kim ◽  
David E. Somers
Keyword(s):  
Circadian Rhythms ◽  
Recent Work ◽  
Transcriptional Control ◽  
Circadian System ◽  
Circadian Oscillator ◽  
Circadian Regulation ◽  
Circadian Control ◽  
Wide Range ◽  
Molecular Components ◽  
Translational Mechanisms

The molecular components of the circadian system possess the interesting feature of acting together to create a self-sustaining oscillator, while at the same time acting individually, and in complexes, to confer phase-specific circadian control over a wide range of physiological and developmental outputs. This means that many circadian oscillator proteins are simultaneously also part of the circadian output pathway. Most studies have focused on transcriptional control of circadian rhythms, but work in plants and metazoans has shown the importance of post-transcriptional and post-translational processes within the circadian system. Here we highlight recent work describing post-translational mechanisms that impact both the function of the oscillator and the clock-controlled outputs.

Lipid metabolism and mitochondria: Cross talk in cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Anubhav Srivastava ◽  
Pransu Srivastava ◽  
Shashank Mathur ◽  
Sabiya Abbas ◽  
Neeraj Rai ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Acid Synthesis ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Metastatic Progression ◽  
Mitochondrial Regulation ◽  
New Therapeutic Approaches ◽  
Therapeutic Regime

: Metabolic reprogramming is considered a major event in cancer initiation, progression and metastasis. The metabolic signature of cancer cells includes alterations in glycolysis, mitochondrial respiration, fatty acid/lipid and amino acid metabolism. Being at a junction of various metabolic pathways, mitochondria play a key role in fueling cancer growth through regulating bioenergetics, metabolism and cell death. Increasing evidence suggests that alteration in lipid metabolism is a common feature of metastatic progression, including fatty acid synthesis as well as fatty acid oxidation. However, the interplay between lipid metabolism and mitochondria in carcinogenesis remains obscure. The present review focuses on key lipid metabolic pathways associated with mitochondrial regulation that drive cancer phenotype and metastasis. We also review potential targets of lipid metabolism and mitochondria to improve the therapeutic regime in cancer patients. This review aims to improve our current understanding of the intricate relation of lipids with mitochondria and provides insights into new therapeutic approaches.

scholarly journals Functional Comparison of High and Low Molecular Weight Chitosan on Lipid Metabolism and Signals in High-Fat Diet-Fed Rats

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 251 ◽  
Author(s):  
Shing-Hwa Liu ◽  
Chen-Yuan Chiu ◽  
Ching-Ming Shi ◽  
Meng-Tsan Chiang
Keyword(s):  
Molecular Weight ◽  
Lipid Metabolism ◽  
Regulatory Element ◽  
Lipid Absorption ◽  
Liver Fat ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Expressions

The present study examined and compared the effects of low- and high-molecular weight (MW) chitosan, a nutraceutical, on lipid metabolism in the intestine and liver of high-fat (HF) diet-fed rats. High-MW chitosan as well as low-MW chitosan decreased liver weight, elongated the small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in rats fed with HF diets. Supplementation of both high- and low-MW chitosan markedly inhibited the suppressed phosphorylated adenosine monophosphate (AMP)-activated protein kinase-α (AMPKα) and peroxisome proliferator-activated receptor-α (PPARα) protein expressions, and the increased lipogenesis/cholesterogenesis-associated protein expressions [peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element binding protein-1c and -2 (SREBP1c and SREBP2)] and the suppressed apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of rats fed with HF diets. Supplementation with both a low- and high-MW chitosan could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein-4 (Angptl4) expression in the intestines of rats fed with HF diets. In comparison between low- and high-MW chitosan, high-MW chitosan exhibits a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and an increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

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