scholarly journals SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Teppei Fujikawa ◽  
Carlos M Castorena ◽  
Mackenzie Pearson ◽  
Christine M Kusminski ◽  
Newaz Ahmed ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Metabolic Effects ◽  
Whole Body ◽  
Hypothalamic Nucleus ◽  
Steroidogenic Factor 1 ◽  
Beneficial Effects ◽  
Genetically Engineered Mice ◽  
Regulation Of Metabolism ◽  
The Central Nervous System ◽  
Whole Body Metabolism

Exercise has numerous beneficial metabolic effects. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. However, a role for the CNS in the regulation of metabolism in the context of the exercise remains less clear. Here, using genetically engineered mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the beneficial effects of exercise on metabolism. We found that VMH-specific deletion of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and (c) increases in energy expenditure that are associated with exercise training. Unexpectedly, we found that SF-1 deletion in the VMH attenuates metabolic responses of skeletal muscle to exercise, including induction of PGC-1α expression. Collectively, this evidence suggests that SF-1 expression in VMH neurons is required for the beneficial effects of exercise on metabolism.

scholarly journals Adiponectin Role in Neurodegenerative Diseases: Focus on Nutrition Review

2020 ◽  
Vol 21 (23) ◽  
pp. 9255
Author(s):  
Rita Polito ◽  
Irene Di Meo ◽  
Michelangela Barbieri ◽  
Aurora Daniele ◽  
Giuseppe Paolisso ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
The Central Nervous System ◽  
Regulatory Effects ◽  
Nutrition Review ◽  
Selective Process

Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin’s role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the “gut-brain” axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.

Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites?

1997 ◽  
Vol 273 (5) ◽  
pp. R1580-R1584 ◽  
Author(s):  
Patrice G. Guyenet
Keyword(s):  
Binding Sites ◽  
Hypotensive Effect ◽  
Genetically Engineered ◽  
Therapeutic Effects ◽  
Genetically Engineered Mice ◽  
Wide Range ◽  
The Central Nervous System ◽  
Imidazoline Binding Sites ◽  
Cellular Components

Clonidine and related α2-adrenergic receptor (α2AR) agonists lower arterial pressure primarily by an action within the central nervous system. These drugs also have varying degrees of affinity for other cellular components called nonadrenergic imidazoline binding sites (NAIBS). For over 20 years, the α2AR agonist activity of clonidine-like drugs was thought to account for their therapeutic effects (α2 theory). However, several groups have recently proposed a competing “imidazoline theory” according to which the hypotensive effect of clonidine-like drugs would in fact owe more to their affinity for one type of NAIBS, called I1receptors. The α2-theory is strongly supported by four main types of congruent data. First, the hypotensive effect of systemically administered clonidine is blocked by α2AR antagonists that are without affinity for I1 NAIBs. Second, the hypotensive effect of intravenous clonidine is absent in genetically engineered mice in which a defective α2AAR has been substituted for the normal one. Third, the sympatholytic effect of clonidine is consistent with the presence of conventional inhibitory α2ARs on sympathetic preganglionic neurons and on their main excitatory inputs in the medulla oblongata. Fourth, the first I1 ligand without affinity for α2ARs was found to be biologically inactive. The imidazoline theory is supported by a limited repertoire of whole animal “in vivo” pharmacological experiments that remain open to a wide range of interpretations. In conclusion, the bulk of the evidence strongly supports a largely predominant role of α2AR mechanisms in the action of most clonidine-like agents at therapeutically relevant doses or concentrations. Even the small pharmacological differences between these agents cannot yet be linked with certainty to their relative affinity for I1 NAIBS.

scholarly journals Interactive Roles for AMPK and Glycogen from Cellular Energy Sensing to Exercise Metabolism

2018 ◽  
Vol 19 (11) ◽  
pp. 3344 ◽  
Author(s):  
Natalie Janzen ◽  
Jamie Whitfield ◽  
Nolan Hoffman
Keyword(s):  
Glycogen Storage ◽  
Experimental Models ◽  
Whole Body ◽  
Carbohydrate Binding ◽  
Tissue Storage ◽  
Ampk Signaling ◽  
Cellular Energy ◽  
Beneficial Effects ◽  
Whole Body Metabolism ◽  
Energy Sensing

The AMP-activated protein kinase (AMPK) is a heterotrimeric complex with central roles in cellular energy sensing and the regulation of metabolism and exercise adaptations. AMPK regulatory β subunits contain a conserved carbohydrate-binding module (CBM) that binds glycogen, the major tissue storage form of glucose. Research over the past two decades has revealed that the regulation of AMPK is impacted by glycogen availability, and glycogen storage dynamics are concurrently regulated by AMPK activity. This growing body of research has uncovered new evidence of physical and functional interactive roles for AMPK and glycogen ranging from cellular energy sensing to the regulation of whole-body metabolism and exercise-induced adaptations. In this review, we discuss recent advancements in the understanding of molecular, cellular, and physiological processes impacted by AMPK-glycogen interactions. In addition, we appraise how novel research technologies and experimental models will continue to expand the repertoire of biological processes known to be regulated by AMPK and glycogen. These multidisciplinary research advances will aid the discovery of novel pathways and regulatory mechanisms that are central to the AMPK signaling network, beneficial effects of exercise and maintenance of metabolic homeostasis in health and disease.

scholarly journals Nonmetastatic Colon Cancer Model C26 Upregulates Glycolysis in Osteocytes in Vitro and Bone in Vivo

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
M. Roarke Tollar ◽  
Matthew Prideaux ◽  
Fabrizio Pin ◽  
Lynda F. Bonewald
Keyword(s):  
Gene Expression ◽  
Culture Media ◽  
Bone Mineralization ◽  
Metabolic Effects ◽  
Whole Body ◽  
Rt Pcr ◽  
Systemic Complications ◽  
Whole Body Metabolism

Background: Developing effective treatments for musculoskeletal complications in cancer patients requires understanding metabolic effects of cancer on bone, and particularly osteocytes, the most abundant bone cell and key regulator of bone remodeling. However, little is known regarding how cancer impacts normal osteocyte energy metabolic pathways, such as glycolysis. Given that changes in metabolism are important regulators of cellular function, it is essential to determine how osteocyte metabolism is disrupted by cancer and how this may impact skeletal and whole-body health. Methods: Mice inoculated with saline (N=5) or C26 cells (N=6) were sacrificed after 2 weeks. Bones were harvested for metabolic profiling by GC-MS, gene expression by RT-PCR and bone morphology by µCT. Differentiated IDG-SW3 osteocyte-like cells were cocultured with C26 cells for 12-24hrs and metabolites and gene expression analyzed by GC-MS and RT-PCR. Results: Trabecular bone mass was significantly decreased in the C26 mice. GC-MS analysis revealed decreased glucose in C26 mice tibiae, but no change in lactate. The bone resorption promoting gene Rankl was upregulated, whereas the inhibitor Opg was unchanged. Bone mineralization regulators Mepe and Phex were decreased. In vitro metabolic studies revealed increased glucose and lactate in IDG-SW3 cell lysate; culture media glucose levels were decreased whereas lactate was increased in the co-cultures with C26 cells. RT-PCR demonstrated increases in the glycolysis promoter Hif1α in addition to glycolysis pathway genes including Glut1, Hk2, Slc16a3 and Pdk1. Rankl was also increased in the IDG-SW3 cells co-cultured with the C26 cells whereas Opg, Phex, and Mepe were downregulated. Conclusion: Glycolysis is upregulated in mouse bone and in vitro IDG-SW3 cells exposed to cancer. Our study provides novel understanding for how cancer affects bone metabolism. Integrating these results with whole body metabolism will aid in the development of novel therapeutic strategies to target musculoskeletal and systemic complications of cancer.

scholarly journals In Vivo Metabolic Roles of G Proteins of the Gi Family Studied with Novel Mouse Models

Endocrinology ◽  
2021 ◽  
Author(s):  
Jürgen Wess
Keyword(s):  
G Proteins ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Genetically Engineered ◽  
Whole Body ◽  
Heterotrimeric G Proteins ◽  
Structural And Functional Properties ◽  
Genetically Engineered Mice

Abstract G protein-coupled receptors (GPCRs) are the target of ~30-35% of all FDA-approved drugs. The individual members of the GPCR superfamily couple to one or more functional classes of heterotrimeric G proteins. The physiological outcome of activating a particular GPCR in vivo depends on the pattern of receptor distribution and the type of G proteins activated by the receptor. Based on the structural and functional properties of their α-subunits, heterotrimeric G proteins are subclassified into four major families: Gs, Gi/o, Gq/11, and G12/13. Recent studies with genetically engineered mice have yielded important novel insights into the metabolic roles of Gi/o-type G proteins. For example, recent data indicate that Gi signaling in pancreatic α-cells plays a key role in regulating glucagon release and whole body glucose homeostasis. Receptor-mediated activation of hepatic Gi signaling stimulates hepatic glucose production, suggesting that inhibition of hepatic Gi signaling could prove clinically useful to reduce pathologically elevated blood glucose levels. Activation of adipocyte Gi signaling reduces plasma free fatty acid levels, thus leading to improved insulin sensitivity in obese, glucose-intolerant mice. These new data suggest that Gi-coupled receptors that are enriched in metabolically important cell types represent potential targets for the development of novel drugs useful for the treatment of type 2 diabetes and related metabolic disorders.

scholarly journals Estrogen: An Emerging Regulator of Insulin Action and Mitochondrial Function

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Anisha A. Gupte ◽  
Henry J. Pownall ◽  
Dale J. Hamilton
Keyword(s):  
Estrogen Receptor ◽  
Insulin Action ◽  
Animal Studies ◽  
Experimental Studies ◽  
Fat Distribution ◽  
Metabolic Effects ◽  
Whole Body ◽  
Current State ◽  
Rapid Changes ◽  
Whole Body Metabolism

Clinical trials and animal studies have revealed that loss of circulating estrogen induces rapid changes in whole body metabolism, fat distribution, and insulin action. The metabolic effects of estrogen are mediated primarily by its receptor, estrogen receptor-α; however, the detailed understanding of its mechanisms is incomplete. Recent investigations suggest that estrogen receptor-αelicits the metabolic effects of estrogen by genomic, nongenomic, and mitochondrial mechanisms that regulate insulin signaling, substrate oxidation, and energetics. This paper reviews clinical and experimental studies on the mechanisms of estrogen and the current state of knowledge regarding physiological and pathobiological influences of estrogen on metabolism.

scholarly journals Prebiotic Functions of Mannose Oligosaccharides Revealed by Microbiomic and Metabolomic Analyses of Intestinal Digesta (P20-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yiwei Ma ◽  
Chi Chen
Keyword(s):  
Growth Performance ◽  
Body Weight Gain ◽  
Sensu Stricto ◽  
Whole Body ◽  
Liquid Chromatography Mass Spectrometry ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Rrna Sequencing ◽  
Whole Body Metabolism ◽  
Induced Changes

Abstract Objectives Mannose oligosaccharides (MOS) are considered to be prebiotics, but MOS-induced changes in the microbiome and metabolome of intestinal digesta were not well characterized. The objective of this study aims to investigate the effects of MOS-induced changes in metabolites and microbiota. Methods 4 groups of male C57Bl/6 mice were fed AIN93G diet containing 0, 0.2, 1 and 5% of MOS, respectively, for six weeks. The effects of MOS on growth performance was determined by body weight gain and food intake. The effects of MOS on the microbiome and metabolome of intestinal digesta were determined by 16S rRNA sequencing and liquid chromatography-mass spectrometry-based metabolomics analysis of ileal, cecal, colonic digesta and feces samples collected at the end of 6-week MOS feeding, respectively. Results MOS feeding did not affect growth performance among different treatments. Microbiomic analysis showed that MOS dose-dependently modulated the microbiome in both cecal and colonic digesta samples. At the phylum level, MOS decreased the abundance of Firmicutes and increased the abundance of Actinobacteria. At the genus level, MOS increased Bacteroides, Parasutterella, Prevotellaceae UCG-001 and decreased Clostridium sensu stricto. Metabolomic analysis showed that MOS dose-dependently affected diverse metabolites from both endogenous and microbial metabolism, including the increases of aspartate, glutamate, lactate, succinate, α-ketoglutarate, butyrate and valerate, and the decreases of many other amino acids. In addition, the correlations between MOS-responsive microbiota and MOS-responsive metabolites were also observed. Conclusions Overall, our results revealed the probiotic functions of MOS by identifying MOS-induced changes in gut microbiome and metabolome, which may provide mechanistic insights on the potential beneficial effects of MOS on the whole-body metabolism system. Funding Sources N/A.

scholarly journals MGAT2 deficiency and vertical sleeve gastrectomy have independent metabolic effects in the mouse

2014 ◽  
Vol 307 (11) ◽  
pp. E1065-E1072 ◽  
Author(s):  
Joram D. Mul ◽  
Denovan P. Begg ◽  
April M. Haller ◽  
Josh W. Pressler ◽  
Joyce Sorrell ◽  
...  
Keyword(s):  
Body Weight ◽  
Sleeve Gastrectomy ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Lipid Synthesis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Vertical Sleeve Gastrectomy ◽  
Beneficial Effects ◽  
Reduced Body

Vertical sleeve gastrectomy (VSG) is currently one of the most effective treatments for obesity. Despite recent developments, the underlying mechanisms that contribute to the metabolic improvements following bariatric surgery remain unresolved. VSG reduces postprandial intestinal triglyceride (TG) production, but whether the effects of VSG on intestinal metabolism are related to metabolic outcomes has yet to be established. The lipid synthesis enzyme acyl CoA:monoacylglycerol acyltransferase-2 ( Mogat2; MGAT2) plays a crucial role in the assimilation of dietary fat in the intestine and in regulation of adiposity stores as well. Given the phenotypic similarities between VSG-operated and MGAT2-deficient animals, we reasoned that this enzyme could also have a key role in mediating the metabolic benefits of VSG. However, VSG reduced body weight and fat mass and improved glucose metabolism similarly in whole body MGAT2-deficient ( Mogat2−/−) mice and wild-type littermates. Furthermore, along with an increase in energy expenditure, surgically naive Mogat2−/− mice had altered macronutrient preference, shifting preference away from fat and toward carbohydrates, and increased locomotor activity. Collectively, these data suggest that the beneficial effects of VSG on body weight and glucose metabolism are independent of MGAT2 activity and rather that they are separate from the effects of MGAT2 deficiency. Because MGAT2 inhibitors are proposed as a pharmacotherapeutic option for obesity, our data suggest that, in addition to increasing energy expenditure, shifting macronutrient preference away from fat could be another important mechanism by which these compounds could contribute to weight loss.

scholarly journals Ceramide Synthase 6 Knockout Reprograms Energy Metabolism in Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 488-488
Author(s):  
Keri Barron ◽  
Natalia Krupenko
Keyword(s):  
Dietary Intervention ◽  
Metabolic Effects ◽  
Whole Body ◽  
Caloric Content ◽  
Significant Shift ◽  
Light Cycle ◽  
Ceramide Synthase ◽  
Bioactive Lipids ◽  
High Fat ◽  
Whole Body Metabolism

Abstract Objectives Ceramides, a group of bioactive lipids and important signaling molecules, have been implicated in the development of cardiometabolic disease, diabetes, and cancer. Recent studies have shown that targeting Ceramide Synthases (CerS), the enzymes producing ceramides, protected from glucose intolerance and diet induced obesity. We investigated metabolomic responses to high fat diet consumption in livers and plasma of wild type (WT) and CerS6 knockout (KO) mice to obtain mechanistic understanding of the protection provided by the enzyme knockout. Methods Upon weaning, male WT and CerS6 KO mice were placed on a high fat (HFD) or control (Ctrl) diet for 16 weeks. After 14 weeks on diet, mice were placed in calorimetry cages for 48 hours. Body composition was assessed before dietary intervention and before necropsy. Plasma and snap-frozen liver samples were subjected to untargeted metabolomic analysis at Metabolon®. Results CerS6 KO mice gained significantly less weight on HFD than WT mice. Calorimetry measurements revealed that over 24 hours CerS6 KO mice did not move more than WT in either x-, y- or z-planes. Interestingly, CerS6 KO mice on a HFD consumed significantly less food, and despite the higher caloric content of the diet, they also consumed fewer calories over the 24 hour period. No differences in fat excretion between WT and CerS6 KO mice were found, measured by fecal lipid content. Calorimetry data demonstrated that on HFD, regardless of genotype, animals oxidized fat for energy. On the Ctrl diet WT mice burned a mix of substrates while CerS6 KO mice preferentially oxidized glucose for energy during the light cycle. This indicates that during the active phase of the light cycle a switch in energy source occurred in KO but not WT mice. Untargeted metabolomics revealed significant differences in intermediates of glycolysis both in liver and plasma of the KO vs WT animals. Moreover, significant increases in multiple TCA cycle metabolites in KO vs WT plasma were seen in HFD fed mice. Conclusions We found a significant shift in tissue-level and whole-body energetics in CerS6 KO mice. This shift could be responsible for the beneficial metabolic effects of targeting CerS6 when HFD is consumed. Further studies will help determine how CerS6 and ceramides influence tissue and whole body metabolism. Funding Sources This work was funded by R01 CA193782 grant to NK.

Metabolic effects of cigarette smoking

1992 ◽  
Vol 72 (2) ◽  
pp. 401-409 ◽  
Author(s):  
K. A. Perkins
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoking ◽  
Acute Effect ◽  
Metabolic Effects ◽  
Whole Body ◽  
Chronic Effect ◽  
Nicotine Intake ◽  
Prediction And Control ◽  
Whole Body Metabolism ◽  
And Control

The inverse relationship between cigarette smoking and body weight, a potent obstacle to stopping smoking, may be due in part to effects of smoking on increasing whole body metabolism. Studies examining chronic and acute metabolic effects of smoking, as well as its constituent nicotine, are reviewed. Evidence suggests the absence of a chronic effect; most studies indicate that smokers and nonsmokers have similar resting metabolic rates (RMR) and that RMR declines very little after smoking cessation. Although an acute effect due to smoking is apparent, its magnitude is inconsistent across studies, possibly because of variability in smoke exposure or nicotine intake. In smokers at rest, the acute effect of smoking (and nicotine intake) appears to be significant but small (less than 10% of RMR) and transient (less than or equal to 30 min). However, the specific situations in which smokers tend to smoke may mediate the magnitude of this effect, inasmuch as smoking during casual physical activity may enhance it while smoking after eating may reduce it. Sympathoadrenal activation by nicotine appears to be primarily responsible for the metabolic effect of smoking, but possible contributions from nonnicotine constituents of tobacco smoke and behavioral effects of inhaling may also be important. Improved understanding of these metabolic effects may lead to better prediction and control of weight gain after smoking cessation, thus increasing the likelihood of maintaining abstinence.

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