The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15

Aggarwal, Abhishek; Costa, Maria José de Carvalho; Rivero-Gutiérrez, Belén; Ji, Lijuan; Morgan, Stefanie L.; Feldman, Brian J.

doi:10.1016/j.celrep.2017.11.004

Cited by 67 publications

(72 citation statements)

References 45 publications

(54 reference statements)

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“…Regarding single Per1 and Per2 mutants, although fertile, they exhibit lower reproductive success than the control group, as occurs in aged wild-type (WT) mice. The role of Per3 in regulating metabolism and adiposity has also been described in animal studies [74,75]. Per1 and Per2 mutations cause advanced aging [76].…”

Section: Per1 1 2 Andmentioning

confidence: 86%

Circadian Clock, Time-Restricted Feeding and Reproduction

Pan

Taylor

Cohen

et al. 2020

IJMS

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The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

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Section: Per1 1 2 Andmentioning

confidence: 86%

Circadian Clock, Time-Restricted Feeding and Reproduction

Pan

Taylor

Cohen

et al. 2020

IJMS

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“…27 These studies demonstrated that primary APCs contain a circadian clock. 23 However, to our surprise, our further investigations elucidated that expression of the classic core clock component Per1 does not significantly oscillate in APCs. 23 Strikingly, we discovered that Per3, has the most robust circadian expression profile of the Per paralogs in primary APCs.…”

Section: Resultsmentioning

confidence: 75%

“…23 However, to our surprise, our further investigations elucidated that expression of the classic core clock component Per1 does not significantly oscillate in APCs. 23 Strikingly, we discovered that Per3, has the most robust circadian expression profile of the Per paralogs in primary APCs. 23 These findings suggested to us that Per3 might have a particularly prominent role in the context of APC biology.…”

Section: Resultsmentioning

confidence: 75%

“…[17][18][19][20] Another example of a metabolically relevant biological process that is influenced by peripheral circadian clocks is adipogenesis-a differentiation pathway where adipocyte precursor cells develop into mature adipocytes. [21][22][23] Dysregulated adipogenesis contributes to expansion of adipocyte tissue and thus is often implicated in obesity. 21 Furthermore, disruption of circadian rhythms is a riskfactor for obesity.…”

Section: Introductionmentioning

confidence: 99%

“…1,24 To begin to exam the mechanisms by which the circadian clock is connected to adipogenesis, previous studies employed in vitro adipocyte differentiation protocols using mouse embryonic fibroblasts cells (MEFs) and immortalized 3T3-L1 cells, e.g.. 25 Recently, we performed studies using primary adipocyte precursor CONTACT Brian J. Feldman feldman@stanford.edu cells (APCs) and approaches that monitor adipogenesis in vivo to establish the presence of peripheral clocks in bona fide APCs and mechanisms by which the circadian clock regulates the process of adipogenesis. 23…”

Section: Introductionmentioning

confidence: 99%

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A context-specific circadian clock in adipocyte precursor cells modulates adipogenesis

Jung

Feldman

2018

Adipocyte

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The circadian clock is an intricate molecular network that paces a variety of physiological process to ~ 24 hour day/night cycles. Whereas the central circadian clock in the brain is primarily entrained by light signals, peripheral circadian clocks, which are in most cells in the body, receive cues not only from the central pacemaker but also endocrine and other systemic and tissue-specific signals. Prior studies have connected peripheral circadian clocks to metabolism, primarily with studies focused on the robust clock in the liver that responds to feeding/fasting cycles. Adipose tissue is also critical for metabolism and adipocytes have circadian clocks. Yet, the role of the circadian clock in adipocytes is poorly understood. Here we describe our studies that revealed components of the circadian clock in primary adipocyte precursor cells (APCs) in mice. We made the surprising discovery of a particularly prominent role for the circadian gene Period 3 (Per3) in the APC clock. Furthermore, we elucidated that Per3 directly regulates an output pathway of the APC clock to modulate the expression of the Kruppel-like factor 15 (Klf15) gene. Finally, we discovered that this clock-Klf15 pathway regulates adipogenesis in APCs. These finding have important implications for our understanding of adipose tissue biology and metabolism and, we speculate, will generate opportunities to develop novel therapeutic strategies based on the context-specific features of the circadian clock in APCs.

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Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review

Shyh‐Chang

et al. 2022

J cachexia sarcopenia muscle

222

131

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Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

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The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15

Cited by 67 publications

References 45 publications

Circadian Clock, Time-Restricted Feeding and Reproduction

Circadian Clock, Time-Restricted Feeding and Reproduction

A context-specific circadian clock in adipocyte precursor cells modulates adipogenesis

Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review

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