scholarly journals Metabolic homeostasis: it’s all in the timing

Endocrinology ◽  
2021 ◽  
Author(s):  
Patricia L Brubaker ◽  
Alexandre Martchenko
Keyword(s):  
Metabolic Disease ◽  
Circadian Clock ◽  
Pancreatic Beta Cell ◽  
Critical Role ◽  
Gut Hormones ◽  
Circadian Regulation ◽  
Metabolic Homeostasis ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
Positive And Negative Feedback

Abstract Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This Mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate Mini-review in this collation of articles published in Endocrinology in 2020/2021, by: Martchenko et al. (Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones); Alvarez et al. (The Microbiome as a Circadian Coordinator of Metabolism); Seshadri et al. (Circadian Regulation of the Pancreatic Beta Cell); McCommis et al. (The Importance of Keeping Time in the Liver); Oosterman et al. (The Circadian Clock, Shift Work, and Tissue-Specific Insulin Resistance); and Heyde et al. (Contributions of White and Brown Adipose Tissues to the Circadian Regulation of Energy Metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in the maintenance of metabolic homeostasis.

scholarly journals Interactions between endocrine and circadian systems

2013 ◽  
Vol 52 (1) ◽  
pp. R1-R16 ◽  
Author(s):  
Anthony H Tsang ◽  
Johanna L Barclay ◽  
Henrik Oster
Keyword(s):  
Cognitive Performance ◽  
Hormonal Regulation ◽  
Circadian Clocks ◽  
Circadian Regulation ◽  
Metabolic Homeostasis ◽  
Peripheral Tissues ◽  
Hormonal Factors ◽  
Circadian Timing ◽  
Downstream Processes ◽  
The Brain

In most species, endogenous circadian clocks regulate 24-h rhythms of behavior and physiology. Clock disruption has been associated with decreased cognitive performance and increased propensity to develop obesity, diabetes, and cancer. Many hormonal factors show robust diurnal secretion rhythms, some of which are involved in mediating clock output from the brain to peripheral tissues. In this review, we describe the mechanisms of clock–hormone interaction in mammals, the contribution of different tissue oscillators to hormonal regulation, and how changes in circadian timing impinge on endocrine signalling and downstream processes. We further summarize recent findings suggesting that hormonal signals may feed back on circadian regulation and how this crosstalk interferes with physiological and metabolic homeostasis.

scholarly journals A Receptor-type Guanylyl Cyclase Expression Is Regulated under Circadian Clock in Peripheral Tissues of the Silk Moth

2001 ◽  
Vol 276 (50) ◽  
pp. 46765-46769 ◽  
Author(s):  
Shintarou Tanoue ◽  
Takaaki Nishioka
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Guanylyl Cyclase ◽  
Dark Period ◽  
Light Period ◽  
Receptor Type ◽  
Circadian Regulation ◽  
Peripheral Tissues ◽  
Silk Moth ◽  
Flight Muscles

The mechanisms by which the circadian clock controls behavior through regulating gene expression in peripheral tissues are largely unknown. Here we demonstrate that the expression of a receptor-type guanylyl cyclase (BmGC-I) from the silk mothBombyx moriis regulated in the flight muscles in a circadian fashion.BmGC-ImRNA was expressed from the end of the light period through the middle of the dark period. BmGC-I protein expression and cGMP levels were high around the initiation of eclosion events at the beginning of the photoperiod. The rhythm of theBmGC-Iand cGMP levels free-ran in constant light and synchronized to the environmental photoperiodic cycle. The circadian regulation of BmGC-I expression was also observed in the legs but not in other tissues examined. BmGC-I therefore represents a circadian output gene that regulates eclosion behavior.

scholarly journals Nutritional approaches for managing obesity-associated metabolic diseases

2017 ◽  
Vol 233 (3) ◽  
pp. R145-R171 ◽  
Author(s):  
Rachel Botchlett ◽  
Shih-Lung Woo ◽  
Mengyang Liu ◽  
Ya Pei ◽  
Xin Guo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Fat Deposition ◽  
Low Grade ◽  
Metabolic Homeostasis ◽  
Peripheral Tissues ◽  
Metabolic Dysregulation

Obesity is an ongoing pandemic and serves as a causal factor of a wide spectrum of metabolic diseases including diabetes, fatty liver disease, and cardiovascular disease. Much evidence has demonstrated that nutrient overload/overnutrition initiates or exacerbates inflammatory responses in tissues/organs involved in the regulation of systemic metabolic homeostasis. This obesity-associated inflammation is usually at a low-grade and viewed as metabolic inflammation. When it exists continuously, inflammation inappropriately alters metabolic pathways and impairs insulin signaling cascades in peripheral tissues/organs such as adipose tissue, the liver and skeletal muscles, resulting in local fat deposition and insulin resistance and systemic metabolic dysregulation. In addition, inflammatory mediators, e.g., proinflammatory cytokines, and excessive nutrients, e.g., glucose and fatty acids, act together to aggravate local insulin resistance and form a vicious cycle to further disturb the local metabolic pathways and exacerbate systemic metabolic dysregulation. Owing to the critical role of nutrient metabolism in controlling the initiation and progression of inflammation and insulin resistance, nutritional approaches have been implicated as effective tools for managing obesity and obesity-associated metabolic diseases. Based on the mounting evidence generated from both basic and clinical research, nutritional approaches are commonly used for suppressing inflammation, improving insulin sensitivity, and/or decreasing fat deposition. Consequently, the combined effects are responsible for improvement of systemic insulin sensitivity and metabolic homeostasis.

scholarly journals Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism

Endocrinology ◽  
2021 ◽  
Vol 162 (3) ◽  
Author(s):  
Isabel Heyde ◽  
Kimberly Begemann ◽  
Henrik Oster
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Energy Levels ◽  
High Energy ◽  
Circadian Clocks ◽  
Circadian Regulation ◽  
Metabolic Homeostasis ◽  
Brown Adipose ◽  
Releasing Factors

Abstract The term energy metabolism comprises the entirety of chemical processes associated with uptake, conversion, storage, and breakdown of nutrients. All these must be tightly regulated in time and space to ensure metabolic homeostasis in an environment characterized by cycles such as the succession of day and night. Most organisms evolved endogenous circadian clocks to achieve this goal. In mammals, a ubiquitous network of cellular clocks is coordinated by a pacemaker residing in the hypothalamic suprachiasmatic nucleus. Adipocytes harbor their own circadian clocks, and large aspects of adipose physiology are regulated in a circadian manner through transcriptional regulation of clock-controlled genes. White adipose tissue (WAT) stores energy in the form of triglycerides at times of high energy levels that then serve as fuel in times of need. It also functions as an endocrine organ, releasing factors in a circadian manner to regulate food intake and energy turnover in other tissues. Brown adipose tissue (BAT) produces heat through nonshivering thermogenesis, a process also controlled by the circadian clock. We here review how WAT and BAT contribute to the circadian regulation of energy metabolism. We describe how adipose rhythms are regulated by the interplay of systemic signals and local clocks and summarize how adipose-originating circadian factors feed-back on metabolic homeostasis. The role of adipose tissue in the circadian control of metabolism becomes increasingly clear as circadian disruption leads to alterations in adipose tissue regulation, promoting obesity and its sequelae. Stabilizing adipose tissue rhythms, in turn, may help to combat disrupted energy homeostasis and obesity.

scholarly journals Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice

2017 ◽  
Vol 233 (3) ◽  
pp. 307-314 ◽  
Author(s):  
Xiwen Xiong ◽  
Cuicui Zhang ◽  
Yang Zhang ◽  
Rui Fan ◽  
Xinlai Qian ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Knockout Mice ◽  
Genome Stability ◽  
Weight Maintenance ◽  
Critical Role ◽  
Gene Promoter ◽  
Metabolic Homeostasis ◽  
Brown Adipose

SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6-knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6f/f:Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line (Sirt6f/f:Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis.

Sirt5 Plays a Critical Role in Mitochondrial Protein Acylation and Mitochondrial Metabolic Homeostasis in Brown Fat

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 274-OR ◽  
Author(s):  
GUOXIAO WANG ◽  
JESSE G. MEYER ◽  
WEIKANG CAI ◽  
MENGYAO E. LI ◽  
SAMIR SOFTIC ◽  
...  
Keyword(s):  
Critical Role ◽  
Mitochondrial Protein ◽  
Brown Fat ◽  
Metabolic Homeostasis ◽  
Protein Acylation

scholarly journals DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Sasaki ◽  
Margaret E. Eng ◽  
Abigail H. Lee ◽  
Alisa Kostaki ◽  
Stephen G. Matthews
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Guinea Pigs ◽  
Critical Role ◽  
Methylation Status ◽  
Peripheral Tissues ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Increased Risk ◽  
Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

Abstract 041: mTORC1 is Required for Leptin-induced Sympathetic Activation to the Kidney but Not Brown Adipose Tissue

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Balyssa B Bell ◽  
Donald A Morgan ◽  
Kamal Rahmouni
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Critical Role ◽  
Conditional Knockout ◽  
Sympathetic Activation ◽  
Long Term Effects ◽  
Brown Adipose ◽  
Mtorc1 Signaling

The adipocyte-derived hormone leptin plays a critical role in the regulation of energy homeostasis through its action in the brain to decrease food intake and promote energy expenditure by increasing sympathetic nerve activity (SNA) to the thermogenic brown adipose tissue (BAT). Leptin also increases SNA to cardiovascular organs including the kidney and raises arterial pressure. However, it is unclear whether leptin controls regional SNA via conserved or distinct molecular mechanisms. Multiple intracellular pathways have been associated with leptin signaling including the mechanistic target of rapamycin complex 1 (mTORC1), which has been proposed as a critical determinant of leptin action. Here, we assessed the contribution of mTORC1 signaling to leptin-evoked regional sympathetic activation. Simultaneous multifiber recording of renal and BAT SNA in anesthetized C57BL/6J mice showed that intracerebroventricular (ICV) administration of leptin (2μg, n=5) increased both renal (170±34%) and BAT (208±37%) SNA. Interestingly, ICV pre-treatment with the mTORC1 inhibitor (rapamycin, 5ng, n=6) abolished the leptin-induced increase in renal (10±6%, P<0.05 vs controls) but not BAT (226±31%) SNA. Next, we used conditional knockout mice that lack the critical mTORC1 subunit, Raptor, specifically in leptin receptor (LRb)-expressing cells (LRb Cre /Raptor fl/fl ) to determine the long-term effects of disrupting mTORC1 signaling on leptin-evoked increase in regional SNA. We confirmed the inability of leptin to activate mTORC1 signaling in LRb-expressing cells of LRb Cre /Raptor fl/fl mice relative to controls using immunohistochemical staining of phosphorylated ribosomal S6, a downstream target of mTORC1. We observed a significant increase in renal SNA in response to ICV leptin in control mice (127±16%, n=9), but not in LRb Cre /Raptor fl/fl mice (-4±15%, n=9, P<0.05 vs controls). Conversely, ICV leptin-induced increase in BAT SNA was not different in LRb Cre /Raptor fl/fl mice (109±27%, n=5) vs. littermate controls (173±52%, n=4). Our data suggest a critical role for mTORC1 signaling in selectively mediating the cardiovascular sympathetic but not the thermogenic actions of leptin, with important implications for obesity-associated hypertension.

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