Regulation of fatty acid metabolism by cell autonomous circadian clocks: time to fatten up on information?
ABSTRACT Molecular, cellular, and animal-based studies have recently exposed circadian clocks as critical regulators of energy balance. Invariably, mouse models of genetically manipulated circadian clock components display features indicative of altered lipid/fatty acid metabolism, including differential adiposity and circulating lipids. The purpose of this minireview is to provide a comprehensive summary of current knowledge regarding the regulation of fatty acid metabolism by distinct cell autonomous circadian clocks. The implications of these recent findings for cardiometabolic disease and human health are discussed.
- SourceAvailable from: Susana Pasquaré
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- "In addition, changes in catabolic and anabolic pathways were reported to alter liver metabolome and improve nutrient utilization and energy expenditure (Hatori et al., 2012). However, circadian clocks located in the liver and other organs and tissues rule out a series of physiological functions including those relating to lipid metabolism (Asher & Schibler, 2011; Bass & Takahashi, 2010; Bray & Young, 2011; Eckel-Mahan et al., 2012), in all likelihood regardless of food availability, although the phases of the oscillations can be altered. The disruption of the circadian molecular clock may result in a number of metabolic disorders including obesity and diabetes (Durgan & Young, 2010; Froy, 2010; Green et al., 2008; Maury et al., 2010; Sookoian et al., 2008; Takahashi et al., 2008). "
ABSTRACT: The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light–dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.Chronobiology International 08/2014; 32(1). DOI:10.3109/07420528.2014.949734 · 2.88 Impact Factor
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ABSTRACT: Over the past decade, evidence has accumulated from basic science, clinical and epidemiological studies linking circadian mechanisms to adipose tissue biology and its related comorbidities, diabetes, metabolic syndrome and obesity. This review highlights recent in-vitro and in-vivo findings from murine, human and model organism studies. High-fat diets attenuate circadian mechanisms in murine adipose depots and these effects appear to be due to obesity rather than hyperglycemia. Deletion of circadian regulatory genes such as AMPK1 and nocturnin alter the circadian biology of adipose tissue. Unlike the mouse, circadian gene oscillation in human adipose tissue appears to be independent of BMI and diabetes status, suggesting that circadian mechanistic variation occurs across species. Clues for future directions in this emerging field come from studies of the hibernation and torpor state in mammals and infection models involving the Drosophila metabolic organ or 'fat body'. There is a growing consensus that circadian rhythms and metabolism are tightly regulated in adipose tissue and peripheral metabolic organs. Although central mechanisms are critical, autonomous clocks exist within the adipocytes themselves. Future circadian advances are likely to result from the studies of adipose tissue-specific gene deletions.11/2011; 14(6):554-61. DOI:10.1097/MCO.0b013e32834ad94b
- Nature 01/2012; 485:62-68. · 42.35 Impact Factor