scholarly journals Natural Phenolic Compounds Targeting The AMPK Activation For Metabolic Health

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Khoa D.A Nguyen ◽  
Khanh V Doan ◽  
Keyword(s):  
Phenolic Compounds ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Antioxidant Property ◽  
Metabolic Health ◽  
Metabolic Effects ◽  
Whole Body ◽  
Ampk Activation ◽  
Ampk Signaling ◽  
Natural Phenolic Compounds

AMP-activated protein kinase (AMPK) is a cellular energy sensor which plays a crucial role in regulation of whole-body energy homeostasis. Activation of AMPK signaling results in favorable effects on mitochondrial function, autophagy, glucose/lipid metabolism, and insulin sensitivity, making it an important therapeutic target in treatment/prevention of metabolic disorders and cancer. Recently, pharmacological studies of natural phenolic compounds indicated that the benefits on metabolic health of these phytochemicals are not only related to their protogenic antioxidant property but also to their AMPK-activating potential. Due to their diverse structures, identification of phenolic compound molecules which have potential to target the AMPK activation for beneficial metabolic effects may be promising in order to develop novel therapeutics in the prevention and/or treatment of metabolic disorders. In this minireview, we summarize beneficial metabolic outcomes of AMPK activation and discuss the capability of natural polyphenols to activate the AMPK pathway focusing on the phenolic acids as potential lead compounds.

scholarly journals AMPK as a mediator of hormonal signalling

2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase ◽  
Hormonal Signalling

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.

scholarly journals Rho-kinase mediates the anorexigenic action of melanocortin by suppressing AMPK

2019 ◽  
Author(s):  
Sang Soo Kim ◽  
Won Min Hwang ◽  
Won-Mo Yang ◽  
Hyon Lee ◽  
Kyong Soo Park ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Rho Kinase ◽  
Metabolic Effects ◽  
Chow Diet ◽  
Physical Interaction ◽  
Signaling Mechanism ◽  
Ampk Signaling ◽  
Normal Chow

ABSTRACTObjectiveMelanocortin action is essential for the maintenance of energy homeostasis. However, knowledge of the signaling mechanism(s) that mediates the effect of melanocortin remains incomplete.MethodsROCK1 is a key regulator of energy balance in the hypothalamus. To explore the role of ROCK1 in the anorexigenic action of melanocortin, we deleted ROCK1 in MC4R neurons in mice. Next, we studied the metabolic effects of MC4R neuron-specific ROCK1-deficiency and following treatment with α-melanocyte-stimulating hormone (MSH).ResultsHere we show that α-MSH increases Rho-kinase 1 (ROCK1) activity in the hypothalamus. Deficiency of ROCK1 in MC4R-expressing neurons results in increased body weight in mice fed normal chow diet. This is likely due to increased food intake and decreased energy expenditure. Importantly, we find that ROCK1 activation in MC4R expressing neurons is required for melanocortin action, as evidenced by the fact that α– MSH’s ability to suppress food intake is impaired in MC4R neuron-specific ROCK1-deficient mice. To elucidate the mechanism by which ROCK1 mediates melanocortin action, we performedin vitrostudies in hypothalamic cells expressing MC4R. We demonstrate that α–MSH promotes the physical interaction of ROCK1 and Gα12, and this results in suppression of AMPK activity.ConclusionsOur study identifies ROCK1 as a novel mediator of melanocortin’s anorexigenic action and uncover a new MC4R→Gα12→ROCK1→AMPK signaling pathway. Targeting Rho-kinase in MC4R-expressing neurons could provide a new strategy to combat obesity and its related complications.

Rhodiola and salidroside in the treatment of metabolic disorders

2019 ◽  
Vol 19 (19) ◽  
pp. 1611-1626 ◽  
Author(s):  
Xiang-Li Bai ◽  
Xiu-Ling Deng ◽  
Guang-Jie Wu ◽  
Wen-Jing Li ◽  
Si Jin
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Ampk Signaling ◽  
Beneficial Effects

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.

Effects of neuromuscular electrical stimulation on energy expenditure and postprandial metabolism in healthy men

2021 ◽  
Author(s):  
Yung-Chih Chen ◽  
Russell G Davies ◽  
Aaron Hengist ◽  
Harriet A Carroll ◽  
Oliver J Perkin ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Energy Expenditure ◽  
Neuromuscular Electrical Stimulation ◽  
Metabolic Health ◽  
Carbohydrate Oxidation ◽  
Metabolic Effects ◽  
Whole Body ◽  
Healthy Men ◽  
Potential Strategy ◽  
Postprandial Insulin

It is unclear whether NeuroMuscular Electrical Stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 ± 9 y (mean ± SD) with a body mass index 22.3 ± 2.3 kg/m2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomized counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. Mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180–262] kcal/2 h) and STAND trial (178 [164–191] kcal/2 h) than during SIT (159 [150–167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared to SIT (p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared to SIT (16.4 [7.7–25.1], 17 [7–27] & 22.6 [10.8–34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more-pronounced effects seen with NMES. Self-selected NMES is a potential strategy to improve metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty • NMES at a comfortable intensity enhances energy expenditure & carbohydrate oxidation and reduces postprandial insulinemia. • Thus, self-selected NMES represents a potential strategy to improve metabolic health.

scholarly journals Metabolic regulation of female puberty via hypothalamic AMPK–kisspeptin signaling

2018 ◽  
Vol 115 (45) ◽  
pp. E10758-E10767 ◽  
Author(s):  
Juan Roa ◽  
Alexia Barroso ◽  
Francisco Ruiz-Pino ◽  
Maria Jesus Vázquez ◽  
Patricia Seoane-Collazo ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Active Form ◽  
Negative Energy ◽  
Female Rats ◽  
Whole Body ◽  
Delayed Puberty ◽  
Cardiometabolic Health ◽  
Ampk Signaling ◽  
Puberty Onset

Conditions of metabolic distress, from malnutrition to obesity, impact, via as yet ill-defined mechanisms, the timing of puberty, whose alterations can hamper later cardiometabolic health and even life expectancy. AMP-activated protein kinase (AMPK), the master cellular energy sensor activated in conditions of energy insufficiency, has a major central role in whole-body energy homeostasis. However, whether brain AMPK metabolically modulates puberty onset remains unknown. We report here that central AMPK interplays with the puberty-activating gene,Kiss1, to control puberty onset. Pubertal subnutrition, which delayed puberty, enhanced hypothalamic pAMPK levels, while activation of brain AMPK in immature female rats substantially deferred puberty. Virogenetic overexpression of a constitutively active form of AMPK, selectively in the hypothalamic arcuate nucleus (ARC), which holds a key population of Kiss1 neurons, partially delayed puberty onset and reduced luteinizing hormone levels. ARC Kiss1 neurons were found to express pAMPK, and activation of AMPK reduced ARCKiss1expression. The physiological relevance of this pathway was attested by conditional ablation of the AMPKα1 subunit in Kiss1 cells, which largely prevented the delay in puberty onset caused by chronic subnutrition. Our data demonstrate that hypothalamic AMPK signaling plays a key role in the metabolic control of puberty, acting via a repressive modulation of ARC Kiss1 neurons in conditions of negative energy balance.

Central infusion of leptin does not increase AMPK signaling in skeletal muscle of sheep

2011 ◽  
Vol 300 (2) ◽  
pp. R511-R518 ◽  
Author(s):  
Rhianna C. Laker ◽  
Belinda A. Henry ◽  
Glenn D. Wadley ◽  
Iain J. Clarke ◽  
Benedict J. Canny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Food Intake ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Ampk Activation ◽  
Plasma Epinephrine ◽  
Ampk Signaling ◽  
Artificial Cerebrospinal Fluid ◽  
Epinephrine Concentration

In sheep, central leptin infusion reduces food intake and increases energy expenditure in adipose tissue and skeletal muscle. The mechanisms for these peripheral effects of central leptin in sheep are not known but, on the basis of rodent studies, may involve AMPK. In mice, central leptin acutely increases both skeletal muscle AMPK activation and glucose uptake. Thus, to investigate whether these effects exist in higher-order mammals, ovariectomized Corriedale ewes ( n = 4 per group) received a continuous lateral ventricular infusion (60 μl/h) of either leptin (50 μg/h) or artificial cerebrospinal fluid (aCSF; CON) for 8 days. Tritiated glucose (3-3H-glucose) was infused intravenously for calculation of whole body glucose turnover during both acute (6 h) and chronic (7–8 days) leptin/aCSF infusion. Muscle biopsies were also obtained. Leptin infusion reduced ( P < 0.05) food intake and body weight, and it also increased plasma epinephrine concentration at 6 h and 7 days, suggesting increased sympathetic nerve activity. Despite this, and in contrast to rodent studies, central leptin infusion did not increase skeletal muscle AMPKα Thr172 phosphorylation or ACCβ Ser221 phosphorylation. Surprisingly, the glucose rate of appearance (glucose Ra) and rate of disappearance (glucose Rd) were reduced by both acute and chronic leptin infusion. Direct infusion of the AMPK activator 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) into the femoral artery increased skeletal muscle AMPK phosphorylation. In conclusion, although central leptin infusion in sheep caused the predicted reduction in food intake and increases plasma epinephrine concentration, it had no effect on AMPK activation in skeletal muscle and actually reduced glucose disposal. This suggests that there are species differences in the peripheral responses to central leptin infusion.

scholarly journals AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sandra Galic ◽  
Kim Loh ◽  
Lisa Murray-Segal ◽  
Gregory R Steinberg ◽  
Zane B Andrews ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Homeostasis ◽  
Metabolic Stress ◽  
Acid Synthesis ◽  
Whole Body ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Ghrelin Receptor ◽  
Ampk Signaling

AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. AMPK inhibits fatty acid synthesis and promotes fatty acid oxidation by phosphorylation of acetyl-CoA carboxylase (ACC) 1 at Ser79 and ACC2 at Ser212. Using mice with Ser79Ala/Ser212Ala knock-in mutations (ACC DKI) we find that inhibition of ACC phosphorylation leads to reduced appetite in response to fasting or cold exposure. At sub-thermoneutral temperatures, ACC DKI mice maintain normal energy expenditure and thermogenesis, but fail to increase appetite and lose weight. We demonstrate that the ACC DKI phenotype can be mimicked in wild type mice using a ghrelin receptor antagonist and that ACC DKI mice have impaired orexigenic responses to ghrelin, indicating ACC DKI mice have a ghrelin signaling defect. These data suggest that therapeutic strategies aimed at inhibiting ACC phosphorylation may suppress appetite following metabolic stress.

scholarly journals Larval nutrition influences adult fat stores and starvation resistance in Drosophila

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247175
Author(s):  
Niyas Rehman ◽  
Jishy Varghese
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Developmental Stages ◽  
Insulin Signalling ◽  
Larval Growth ◽  
Nutrient Status ◽  
Metabolic Effects ◽  
Adult Size ◽  
Starvation Resistance ◽  
Mature Adult

Insulin plays a major role in connecting nutrient availability to energy homeostasis by regulating metabolic pathways. Defects in insulin signalling is the primary cause for diabetes, obesity and various metabolic disorders. Nutritional status during growth and developmental stages play a crucial role in determining adult size, fecundity and ageing. However, the association between developmental nutrition and adult metabolic disorders has not been fully explored. Here, we address the effects of nutrient status during the larval growth phase on adult metabolism in Drosophila. We report that restricted food supply in larvae led to higher fat reserves and starvation resistance in mature adult flies, which we attribute to low insulin signalling. A lesser amount of stored fat was mobilised during early adult stages and during acute starvation, which accounts for the metabolic effects. Furthermore, larval diet influenced the expression of fat mobilisation genes brummer and lipid storage droplet-2 in adult flies, which led to the metabolic phenotypes reported here. Thus, the restricted nutrient environment in developing larvae led to adaptive changes that entrain the adult flies for scarce food availability.

scholarly journals A-769662 inhibits adipocyte glucose uptake in an AMPK-independent manner

2021 ◽  
Vol 478 (3) ◽  
pp. 633-646
Author(s):  
Franziska Kopietz ◽  
Yazeed Alshuweishi ◽  
Silvia Bijland ◽  
Fatmah Alghamdi ◽  
Eva Degerman ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Energy Homeostasis ◽  
Inhibitory Effect ◽  
Whole Body ◽  
Ampk Activation ◽  
Independent Manner ◽  
Amp Activated Protein Kinase ◽  
Body Energy ◽  
Site Binding

Activation of AMP-activated protein kinase (AMPK) is considered a valid strategy for the treatment of type 2 diabetes. However, despite the importance of adipose tissue for whole-body energy homeostasis, the effect of AMPK activation in adipocytes has only been studied to a limited extent and mainly with the AMP-mimetic 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), which has limited specificity. The aim of this study was to evaluate the effect of the allosteric AMPK activators A-769662 and 991 on glucose uptake in adipocytes. For this purpose, primary rat or human adipocytes, and cultured 3T3-L1 adipocytes, were treated with either of the allosteric activators, or AICAR, and basal and insulin-stimulated glucose uptake was assessed. Additionally, the effect of AMPK activators on insulin-stimulated phosphorylation of Akt and Akt substrate of 160 kDa was assessed. Furthermore, primary adipocytes from ADaM site binding drug-resistant AMPKβ1 S108A knock-in mice were employed to investigate the specificity of the drugs for the observed effects. Our results show that insulin-stimulated adipocyte glucose uptake was significantly reduced by A-769662 but not 991, yet neither activator had any clear effects on basal or insulin-stimulated Akt/AS160 signaling. The use of AMPKβ1 S108A mutant-expressing adipocytes revealed that the observed inhibition of glucose uptake by A-769662 is most likely AMPK-independent, a finding which is supported by the rapid inhibitory effect A-769662 exerts on glucose uptake in 3T3-L1 adipocytes. These data suggest that AMPK activation per se does not inhibit glucose uptake in adipocytes and that the effects of AICAR and A-769662 are AMPK-independent.

Sign in / Sign up

Export Citation Format

Share Document