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.

scholarly journals Cellular Distribution, Regulated Expression, and Functional Role of the Anorexigenic Peptide, NUCB2/Nesfatin-1, in the Testis

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1959-1971 ◽  
Author(s):  
D. García-Galiano ◽  
R. Pineda ◽  
T. Ilhan ◽  
J. M. Castellano ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Functional Role ◽  
Energy Homeostasis ◽  
Ex Vivo ◽  
Whole Body ◽  
Mrna Levels ◽  
Gonadal Function ◽  
Human Choriogonadotropin ◽  
Puberty Onset

Nesfatin-1, product of the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as anorectic hypothalamic neuropeptide, acting in a leptin-independent manner. In addition to its central role in the control of energy homeostasis, evidence has mounted recently that nesfatin-1 is also produced in peripheral metabolic tissues, such as pancreas, adipose, and gut. Moreover, nesfatin-1 has been shown to participate in the control of body functions gated by whole-body energy homeostasis, including puberty onset. Yet, whether, as is the case for other metabolic neuropeptides, NUCB2/nesfatin-1 participates in the direct control of gonadal function remains unexplored. We document here for the first time the expression of NUCB2 mRNA in rat, mouse, and human testes, where NUCB2/nesfatin-1 protein was identified in interstitial mature Leydig cells. Yet in rats, NUCB2/nesfatin-1 became expressed in Sertoli cells upon Leydig cell elimination and was also detected in Leydig cell progenitors. Although NUCB2 mRNA levels did not overtly change in rat testis during pubertal maturation and after short-term fasting, NUCB2/nesfatin-1 content significantly increased along the puberty-to-adult transition and was markedly suppressed after fasting. In addition, testicular NUCB2/nesfatin-1 expression was up-regulated by pituitary LH, because hypophysectomy decreased, whereas human choriogonadotropin (super-agonist of LH receptors) replacement enhanced, NUCB2/nesfatin-1 mRNA and peptide levels. Finally, nesfatin-1 increased human choriogonadotropin-stimulated testosterone secretion by rat testicular explants ex vivo. Our data are the first to disclose the presence and functional role of NUCB2/nesfatin-1 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues as well as by Leydig cell-derived factors. Our observations expand the reproductive dimension of nesfatin-1, which may operate directly at the testicular level to link energy homeostasis, puberty onset, and gonadal function.

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.

Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning

2020 ◽  
Vol 40 (1) ◽  
pp. 25-49 ◽  
Author(s):  
Nishan Sudheera Kalupahana ◽  
Bimba Lakmini Goonapienuwala ◽  
Naima Moustaid-Moussa
Keyword(s):  
Fatty Acids ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Omega 3 ◽  
Brown Adipose ◽  
Body Energy

White adipose tissue (WAT) and brown adipose tissue (BAT) are involved in whole-body energy homeostasis and metabolic regulation. Changes to mass and function of these tissues impact glucose homeostasis and whole-body energy balance during development of obesity, weight loss, and subsequent weight regain. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which have known hypotriglyceridemic and cardioprotective effects, can also impact WAT and BAT function. In rodent models, these fatty acids alleviate obesity-associated WAT inflammation, improve energy metabolism, and increase thermogenic markers in BAT. Emerging evidence suggests that ω-3 PUFAs can also modulate gut microbiota impacting WAT function and adiposity. This review discusses molecular mechanisms, implications of these findings, translation to humans, and future work, especially with reference to the potential of these fatty acids in weight loss maintenance.

scholarly journals The Gastrointestinal Tract as Prime Site for Cardiometabolic Protection by Dietary Polyphenols

2019 ◽  
Vol 10 (6) ◽  
pp. 999-1011 ◽  
Author(s):  
Jose A Villa-Rodriguez ◽  
Idolo Ifie ◽  
Gustavo A Gonzalez-Aguilar ◽  
Diana E Roopchand
Keyword(s):  
Gastrointestinal Tract ◽  
Energy Homeostasis ◽  
Nutritional Epidemiology ◽  
Whole Body ◽  
Cardiometabolic Health ◽  
Biological Mechanisms ◽  
Hormonal Responses ◽  
Dietary Polyphenols ◽  
Body Energy ◽  
Prime Target

ABSTRACT Substantial evidence from nutritional epidemiology links polyphenol-rich diets with reduced incidence of chronic disorders; however, biological mechanisms underlying polyphenol-disease relations remain enigmatic. Emerging evidence is beginning to unmask the contribution of the gastrointestinal tract on whole-body energy homeostasis, suggesting that the intestine may be a prime target for intervention and a fundamental site for the metabolic actions of polyphenols. During their transit through the gastrointestinal tract, polyphenols may activate enteric nutrient sensors ensuing appropriate responses from other peripheral organs to regulate metabolic homeostasis. Furthermore, polyphenols can modulate the absorption of glucose, attenuating exaggerated hormonal responses and metabolic imbalances. Polyphenols that escape absorption are metabolized by the gut microbiota and the resulting catabolites may act locally, activating nuclear receptors that control enteric functions such as intestinal permeability. Finally, polyphenols modulate gut microbial ecology, which can have profound effects on cardiometabolic health.

Intensified exercise training does not alter AMPK signaling in human skeletal muscle

2004 ◽  
Vol 286 (5) ◽  
pp. E737-E743 ◽  
Author(s):  
S. A. Clark ◽  
Z.-P. Chen ◽  
K. T. Murphy ◽  
R. J. Aughey ◽  
M. J. McKenna ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Regulation ◽  
Fat Oxidation ◽  
Whole Body ◽  
Intense Exercise ◽  
Muscle Lactate ◽  
Ampk Signaling ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise ◽  
Resting Muscle

The AMP-activated protein kinase (AMPK) cascade has been linked to many of the acute effects of exercise on skeletal muscle substrate metabolism, as well as to some of the chronic training-induced adaptations. We determined the effect of 3 wk of intensified training (HIT; 7 sessions of 8 × 5 min at 85% V̇o2 peak) in skeletal muscle from well-trained athletes on AMPK responsiveness to exercise. Rates of whole body substrate oxidation were determined during a 90-min steady-state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling were determined from biopsies taken at rest and immediately after exercise during the first and seventh HIT sessions, performed at the same (absolute) pre-HIT work rate. HIT decreased rates of whole body carbohydrate oxidation ( P < 0.05) and increased rates of fat oxidation ( P < 0.05) during SS. Resting muscle glycogen and its utilization during intense exercise were unaffected by HIT. However, HIT induced a twofold decrease in muscle [lactate] ( P < 0.05) and resulted in tighter metabolic regulation, i.e., attenuation of the decrease in the PCr/(PCr + Cr) ratio and of the increase in [AMPfree]/ATP. Resting activities of AMPKα1 and -α2 were similar post-HIT, with the magnitude of the rise in response to exercise similar pre- and post-HIT. AMPK phosphorylation at Thr172 on both the α1 and α2 subunits increased in response to exercise, with the magnitude of this rise being similar post-HIT. Acetyl-coenzyme A carboxylase-β phosphorylation was similar at rest and, despite HIT-induced increases in whole body rates of fat oxidation, did not increase post-HIT. Our results indicate that, in well-trained individuals, short-term HIT improves metabolic control but does not blunt AMPK signaling in response to intense exercise.

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 Effect of perinatal administration of flavonoid-rich extract from Hibiscus sabdariffa to feed-restricted rats, on offspring postnatal growth and reproductive development

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Odochi O. Chukwu ◽  
Chinedum U. Emelike ◽  
Nwaeze G. Konyefom ◽  
Sylvester N. Ibekailo ◽  
Sharon O. Azubuike-Osu ◽  
...  
Keyword(s):  
Reproductive Development ◽  
Postnatal Growth ◽  
Diet Group ◽  
Female Rats ◽  
Delayed Puberty ◽  
Control Group ◽  
Hibiscus Sabdariffa ◽  
Restricted Diet ◽  
Group I ◽  
Puberty Onset

Abstract Developmental programming is a process where stimulus or insult acting during critical periods of growth and development might permanently alter tissue anatomy and physiology so as to produce adverse effects in adult life. Most forms of exposure include maternal nutrient deprivation, nutrient excess, exogenous glucocorticoid excess and endogenous glucocorticoid due to maternal stress. Hibiscus sabdariffa (Hs) are highly rich in phenolic compounds with marked physiological activities, the sweetened aqueous extract of Hs, commonly known as “Zobo’ in Nigeria, is consumed by humans including pregnant and lactating mothers. This study aimed at determining effects of perinatal administration of flavonoid-rich extract from Hs to feed-restricted rats, on offspring postnatal growth and reproductive development. Twenty-five pregnant female rats were used. Rats were randomly placed into five groups of five rats per group (one animal per cage): Group I (Normal control); Group II (feed-restricted control); Group III (5 mg/kg extract + 70% feed-restricted diet); Group IV (10 mg/kg extract + 70% feed-restricted diet); Group V (20 mg/kg extract + 70% feed-restricted diet). Dams were allowed to nurse only 8 pups. Pups were weaned to ad libitum feed and water and were observed daily for puberty onset. Weights, lengths and body mass index (BMI) of pups were measured at delivery, weaning and puberty onset. At onset of puberty in each of the rats, blood samples were collected for determination of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol and testosterone. Reproductive organs were excised and weighed for histology. The extract caused significant increase in postnatal weight, length and BMI of offspring at birth, weaning and puberty onset and significantly delayed puberty onset in both sexes. There was significant increase in absolute and relative weights of testes and ovaries with alterations in histology. This study has shown that maternal consumption of flavonoid-rich extract of Hs during pregnancy and lactation may accelerate offspring postnatal growth with delay in onset of puberty.

Metabolic Regulation of Hippocampal Neuronal Development and Its Inhibition After Irradiation

2021 ◽  
Vol 80 (5) ◽  
pp. 467-475
Author(s):  
Yu-Qing Li ◽  
C Shun Wong
Keyword(s):  
Cell Fate ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Neuronal Development ◽  
Adenosine Monophosphate ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Wild Type ◽  
Newborn Neuron ◽  
Negative Effect

Abstract 5′-Adenosine monophosphate-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, plays a role in cell fate determination. Whether AMPK regulates hippocampal neuronal development remains unclear. Hippocampal neurogenesis is abrogated after DNA damage. Here, we asked whether AMPK regulates adult hippocampal neurogenesis and its inhibition following irradiation. Adult Cre-lox mice deficient in AMPK in brain, and wild-type mice were used in a birth-dating study using bromodeoxyuridine to evaluate hippocampal neurogenesis. There was no evidence of AMPK or phospho-AMPK immunoreactivity in hippocampus. Increase in p-AMPK but not AMPK expression was observed in granule neurons and subgranular neuroprogenitor cells (NPCs) in the dentate gyrus within 24 hours and persisted up to 9 weeks after irradiation. AMPK deficiency in Cre-lox mice did not alter neuroblast and newborn neuron numbers but resulted in decreased newborn and proliferating NPCs. Inhibition of neurogenesis was observed after irradiation regardless of genotypes. In Cre-lox mice, there was further loss of newborn early NPCs and neuroblasts but not newborn neurons after irradiation compared with wild-type mice. These results are consistent with differential negative effect of AMPK on hippocampal neuronal development and its inhibition after irradiation.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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