PER2 Controls Lipid Metabolism by Direct Regulation of PPARγ

Grimaldi, Benedetto; Bellet, Marina Maria; Katada, Sayako; Astarita, Giuseppe; Hirayama, Jun; Amin, Rajesh; Granneman, James G.; Piomelli, Daniele; Leff, Todd; Sassone–Corsi, Paolo

doi:10.1016/j.cmet.2010.10.005

Cited by 423 publications

(357 citation statements)

References 52 publications

Supporting

Mentioning

339

Contrasting

Unclassified

Order By: Relevance

“…In white adipose tissue of Per2 −/− mice, TAG are reduced relative to wild-type mice, whereas higher levels of saturated and monounsaturated very-long-chain fatty acids are observed (111) . A reduction in TAG carrying PUFA has also been reported in white adipose tissue of mice with adipocyte-specific deletion of the Bmal1 gene (75) .…”

Section: Using Lipidomics To Characterise Metabolic Pathwaysmentioning

confidence: 90%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

143

View full text Add to dashboard Cite

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.

show abstract

Section: Using Lipidomics To Characterise Metabolic Pathwaysmentioning

confidence: 90%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

143

View full text Add to dashboard Cite

show abstract

“…Of these 3 proteins, PER2 has been the most studied in terms of metabolism and immunity. Per2-/-mice show a reduction in levels of total triacylglycerol and non-sterified fatty acids [139]. Per2 deletion also leads to enhanced adipocyte differentiation in cultured fibroblasts.…”

Section: The Clock Repressors: Period and Cryptochromementioning

confidence: 99%

“…Per2 deletion also leads to enhanced adipocyte differentiation in cultured fibroblasts. This was due to PER2 mediated suppression of Peroxisome proliferator-activated receptor gamma (PPAR␥), a nuclear receptor that is crucial in adipogenesis [139]. Per3 deletion also leads to enhanced adipogenesis while ectopic expression of PER3 inhibits it [140].…”

Section: The Clock Repressors: Period and Cryptochromementioning

confidence: 99%

“…Il-6 and Tnf˛ RNA. Lower NF-B activation [147] Cry1 (AP-Tg) Global • Elevated glucose levels in serum and urine [161] • Common symptoms of diabetes mellitus, polydipsia and polyuria [161] Per2 Global • Reduced levels of triacylglycerol and non-sterified fatty acids [139] • Enhanced adipocyte differentiation [139] • Increased plasma insulin and impaired gluconeogenesis [142,143] • Protected from sepsis-induced death [144] • Lower IL-1␤ and IFNϒ in serum [144] • Lower Tlr9 expression [82] Per3 Global • Enhanced adipogenesis [139] • Increased adipose tissue and decreased muscle tissue mass [139] Rev-erb˛ Global • Increased adiposity and mild hyperglycemia [119] • Altered lipid and glucose metabolism [119] • Increase in G6Pase and PEPCK [120] • Increased IL-6 in serum [124] ROR˛ sg/sg Global • Reduced adiposity and protection from obesity [128] • Lower serum and liver triglyceride levels [128] • Impaired Th17 cell development [133] • Highly susceptible to LPS induced sepsis [136] ROR Global • Enhanced production of insulin sensitive adipocytes.…”

Section: Bmal1-a Master Regulatormentioning

confidence: 99%

See 1 more Smart Citation

Immunometabolism: Is it under the eye of the clock?

Early

Curtis

2016

Seminars in Immunology

View full text Add to dashboard Cite

“…circadian rhythmicity is associated with hyperlipidemia and hepatic steatosis in ClockΔ19 mice (13), with obesity in mice that bear an adipocyte-specific deletion of Bmal1 (14), and with reduced wholebody weight and reduction of total triglycerides and fatty acids in blood plasma of Per2-deficient mice (15).…”

Section: Significancementioning

confidence: 99%

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Loizides‐Mangold

Perrin

Vandereycken

et al. 2017

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

View full text Add to dashboard Cite

Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.lipid metabolism | circadian clock | human skeletal muscle | human primary myotubes | lipidomics C ircadian oscillations are daily cycles in behavior and physiology that are driven by the existence of underlying intrinsic biological clocks with near 24-h periods. This anticipatory mechanism has evolved to ensure that all aspects of behavior and physiology, including metabolic pathways, are temporally coordinated with daily cycles of rest-activity and feeding to provide the organism with an adaptive advantage (1). In mammals, circadian oscillations are driven by a master pacemaker, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which orchestrates subsidiary oscillators in peripheral organs via neuronal, endocrine, and metabolic signaling pathways (2, 3).Large-scale gene expression datasets suggest that, in mammals, the vast majority of circadian-gene expression is highly organ-specific (4-6). Key metabolic functions in peripheral organs are subject to daily oscillations, such as carbohydrate and lipid metabolism by the liver, skeletal muscle, and endocrine pancreas (7).Skeletal muscle is a major contributor of whole-body metabolism and is the main site of glucose uptake in the postprandial state (8). Therefore, perturbations in glucose sensing and metabolism in skeletal muscle are strongly associated with insulin resistance in type 2 diabetes (T2D) (9). Recent data support a fundamental role for the circadian muscle clock in the regulation of glucose uptake, with a significant re...

show abstract

PER2 Controls Lipid Metabolism by Direct Regulation of PPARγ

Cited by 423 publications

References 52 publications

Circadian regulation of lipid metabolism

Circadian regulation of lipid metabolism

Immunometabolism: Is it under the eye of the clock?

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Contact Info

Product

Resources

About