scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

2009 ◽  
Vol 89 (1) ◽  
pp. 147-191 ◽  
Author(s):  
Philippe Lefebvre ◽  
Bertrand Cariou ◽  
Fleur Lien ◽  
Folkert Kuipers ◽  
Bart Staels
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Bile Acids ◽  
Disease Risk ◽  
Critical Role ◽  
Elevated Serum ◽  
Farnesoid X Receptor ◽  
The Metabolic Syndrome ◽  
Increased Risk

The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be defined as a cluster of cardiovascular disease risk factors including visceral obesity, insulin resistance, dyslipidemia, increased blood pressure, and hypercoagulability. The farnesoid X receptor (FXR) belongs to the superfamily of ligand-activated nuclear receptor transcription factors. FXR is activated by bile acids, and FXR-deficient ( FXR−/−) mice display elevated serum levels of triglycerides and high-density lipoprotein cholesterol, demonstrating a critical role of FXR in lipid metabolism. In an opposite manner, activation of FXR by bile acids (BAs) or nonsteroidal synthetic FXR agonists lowers plasma triglycerides by a mechanism that may involve the repression of hepatic SREBP-1c expression and/or the modulation of glucose-induced lipogenic genes. A cross-talk between BA and glucose metabolism was recently identified, implicating both FXR-dependent and FXR-independent pathways. The first indication for a potential role of FXR in diabetes came from the observation that hepatic FXR expression is reduced in animal models of diabetes. While FXR−/−mice display both impaired glucose tolerance and decreased insulin sensitivity, activation of FXR improves hyperglycemia and dyslipidemia in vivo in diabetic mice. Finally, a recent report also indicates that BA may regulate energy expenditure in a FXR-independent manner in mice, via activation of the G protein-coupled receptor TGR5. Taken together, these findings suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.

scholarly journals The essential role of sodium bioenergetics and ATP homeostasis in the developmental transitions of a cyanobacterium

2020 ◽  
Author(s):  
Sofia Doello ◽  
Markus Burkhardt ◽  
Karl Forchhammer
Keyword(s):  
Energy Homeostasis ◽  
Nitrogen Starvation ◽  
Critical Role ◽  
Quiescent State ◽  
Bacterial Survival ◽  
Bacterial Populations ◽  
Photoautotrophic Growth ◽  
Available Energy ◽  
Atp Levels

The ability to resume growth after a dormant period is an important strategy for the survival and spreading of bacterial populations. Energy homeostasis is critical in the transition into and out of a quiescent state. Synechocystis sp. PCC 6803, a non-diazotrophic cyanobacterium, enters metabolic dormancy as a response to nitrogen starvation. We used Synechocystis as a model to investigate the regulation of ATP homeostasis during dormancy and unraveled a critical role for sodium bioenergetics in dormant cells. During nitrogen starvation, cells reduce their ATP levels and engage sodium bioenergetics to maintain the minimum ATP content required for viability. When nitrogen becomes available, energy requirements rise, and cells immediately increase ATP levels employing sodium bioenergetics and glycogen catabolism. These processes allow them to restore the photosynthetic machinery and resume photoautotrophic growth. Our work reveals a precise regulation of the energy metabolism essential for bacterial survival during periods of nutrient deprivation.

scholarly journals Gene–nutrient interactions in the metabolic syndrome: the role of adiponectin

2008 ◽  
Vol 67 (OCE7) ◽  
Author(s):  
J. F. Ferguson ◽  
C. Phillips ◽  
A. C. Tierney ◽  
J. McMonagle ◽  
J. A. Lovegrove ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome

scholarly journals Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy + Apoe −/− mouse model of the metabolic syndrome

Diabetologia ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 2660-2668 ◽  
Author(s):  
H. G. Martinez ◽  
M. P. Quinones ◽  
F. Jimenez ◽  
C. A. Estrada ◽  
K. Clark ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mouse Model ◽  
Critical Role ◽  
The Metabolic Syndrome ◽  
Apoe Mouse

scholarly journals Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Metabolic Disease ◽  
Kidney Disease ◽  
Maternal Obesity ◽  
Disease Risk ◽  
Reproductive Age ◽  
Intrauterine Environment ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Epigenetic Modulation

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.

scholarly journals Metabolic Disease Risk Alters Circulating Peripheral Blood Mononuclear Cell microRNAs in Response to A High Glycemic Meal

Proceedings ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 30
Author(s):  
Farha Ramzan ◽  
Randall F. D’Souza ◽  
Brenan R. Durainayagam ◽  
Amber M. Milan ◽  
James F. Markworth ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Peripheral Blood Mononuclear Cell ◽  
Mononuclear Cell ◽  
Peripheral Blood ◽  
Disease Risk ◽  
Peripheral Blood Mononuclear ◽  
The Metabolic Syndrome ◽  
Metabolic Disease Risk

Background: High glycemic diets have been shown to exacerbate the risk of cardio-metabolicdisease in individuals with pre-existing disease risk, including obesity and insulin resistance,common to the Metabolic Syndrome (MetS). [...]

Leptin system loss of function in the absence of obesity in zebrafish

2021 ◽  
Author(s):  
Amrutha Bagivalu Lakshminarasimha ◽  
Patrick Page McCaw ◽  
Diana Möckel ◽  
Felix Gremse ◽  
Maximilian Michel
Keyword(s):  
Morbid Obesity ◽  
Crucial Role ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Loss Of Function ◽  
Significant Variance ◽  
Growth Phenotype ◽  
The Difference ◽  
Leptin System

The leptin system plays a crucial role in the regulation of appetite and energy homeostasis in vertebrates. While the phenotype of morbid obesity due to leptin or leptin receptor (lepr) loss of function is well established in mammals, evidence in fish is controversial, questioning the role of leptin as the vertebrate adipostat. Here we report on 3 lepr loss of function (lof) and one leptin loss of function allele in zebrafish. In order to demonstrate that the lepr lof alleles cannot transduce a leptin signal, we measured socs3a transcription after intraperitoneal leptin which is abolished by lepr lof. None of the lepr/lepa lof alleles lead to obesity / a body growth phenotype. We explore possible reasons leading to the difference in published results and find that even slight changes in background genetics such as inbreeding siblings and cousins can lead to significant variance in growth.

scholarly journals Role of leptin receptors in granulosa cells during ovulation

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Lisa Dupuis ◽  
Yasmin Schuermann ◽  
Tamara Cohen ◽  
Dayananda Siddappa ◽  
Anitha Kalaiselvanraja ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Leptin Receptor ◽  
Critical Role ◽  
Follicular Development ◽  
Reproductive Function ◽  
Control Treatment ◽  
Maturation Stage ◽  
Leptin Receptors ◽  
Enhancer Binding Protein

Leptin is an important hormone influencing reproductive function. However, the mechanisms underpinning the role of leptin in the regulation of reproduction remain to be completely deciphered. In this study, our objective is to understand the mechanisms regulating the expression of leptin receptor (Lepr) and its role in ovarian granulosa cells during ovulation. First, granulosa cells were collected from superovulated mice to profile mRNA expression of Lepr isoforms (LeprA and LeprB) throughout follicular development. Expression of LeprA and LeprB was dramatically induced in the granulosa cells of ovulating follicles at 4 h after human chorionic gonadotropin (hCG) treatment. Relative abundance of both mRNA and protein of CCAAT/enhancer-binding protein β (Cebpβ) increased in granulosa cells from 1 to 7 h post-hCG. Furthermore, chromatin immunoprecipitation assay confirmed the recruitment of Cebpβ to Lepr promoter. Thus, hCG-induced transcription of Lepr appears to be regulated by Cebpβ, which led us to hypothesise that Lepr may play a role during ovulation. To test this hypothesis, we used a recently developed pegylated superactive mouse leptin antagonist (PEG-SMLA) to inhibit Lepr signalling during ovulation. I.p. administration of PEG-SMLA (10 μg/g) to superovulated mice reduced ovulation rate by 65% compared with control treatment. Although the maturation stage of the ovulated oocytes remained unaltered, ovulation genes Ptgs2 and Has2 were downregulated in PEG-SMLA-treated mice compared with control mice. These results demonstrate that Lepr is dramatically induced in the granulosa cells of ovulating follicles and this induction of Lepr expression requires the transcription factor Cebpβ. Lepr plays a critical role in the process of ovulation by regulating, at least in part, the expression of the important genes involved in the preovulatory maturation of follicles.

The subfornical organ: a central nervous system site for actions of circulating leptin

2009 ◽  
Vol 296 (3) ◽  
pp. R512-R520 ◽  
Author(s):  
P. M. Smith ◽  
A. P. Chambers ◽  
C. J. Price ◽  
W. Ho ◽  
C. Hopf ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Critical Role ◽  
Subfornical Organ ◽  
Direct Access ◽  
Central Administration ◽  
Energy Status ◽  
Sites Of Action

Adipose tissue plays a critical role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, and neuroendocrine function. Leptin is the prototypic adipokine that acts centrally to signal long-term energy balance. While hypothalamic and brain stem nuclei are well-established sites of action of leptin, we tested the hypothesis that leptin signaling occurs in the subfornical organ (SFO). The SFO is a circumventricular organ (CVO) that lacks the normal blood-brain barrier, is an important site in central autonomic regulation, and has been suggested to have a role in modulating peripheral signals indicating energy status. We report here the presence of mRNA for the signaling form of the leptin receptor in SFO and leptin receptor localization by immunohistochemistry within this CVO. Central administration of leptin resulted in phosphorylation of STAT3 in neurons of SFO. Whole cell current-clamp recordings from dissociated SFO neurons demonstrated that leptin (10 nM) influenced the excitability of 64% (46/72) of SFO neurons. Leptin was found to depolarize the majority of responsive neurons with a mean change in membrane potential of 7.3 ± 0.6 mV (39% of all SFO neurons), while the remaining cells that responded to leptin hyperpolarized (−6.9 ± 0.7 mV, 25% of all SFO neurons). Similar depolarizing and hyperpolarizing effects of leptin were observed in recordings from acutely prepared SFO slice preparations. Leptin was found to influence the same population of SFO neurons influenced by amylin as three of four cells tested for the effects of bath application of both amylin and leptin depolarized to both peptides. These observations identify the SFO as a possible central nervous system location, with direct access to the peripheral circulation, at which leptin may act to influence hypothalamic control of energy homeostasis.

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

2014 ◽  
Vol 307 (1) ◽  
pp. E1-E13 ◽  
Author(s):  
Christopher Lipina ◽  
Andrew J. Irving ◽  
Harinder S. Hundal
Keyword(s):  
Energy Homeostasis ◽  
Endocannabinoid System ◽  
Oxidative Capacity ◽  
Current Evidence ◽  
Peripheral Insulin Resistance ◽  
Physiological Processes ◽  
Peripheral Stimulation ◽  
The Metabolic Syndrome ◽  
Lipid Utilization

The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria, which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilization. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity and, where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.

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