scholarly journals A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takashi Koyama ◽  
Selim Terhzaz ◽  
Muhammad T. Naseem ◽  
Stanislav Nagy ◽  
Kim Rewitz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Energy Homeostasis ◽  
Neurosecretory Cells ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Peripheral Tissues ◽  
Central Node ◽  
Energy Mobilization ◽  
External Conditions ◽  
Adult Drosophila

AbstractAnimals maintain metabolic homeostasis by modulating the activity of specialized organs that adjust internal metabolism to external conditions. However, the hormonal signals coordinating these functions are incompletely characterized. Here we show that six neurosecretory cells in the Drosophila central nervous system respond to circulating nutrient levels by releasing Capa hormones, homologs of mammalian neuromedin U, which activate the Capa receptor (CapaR) in peripheral tissues to control energy homeostasis. Loss of Capa/CapaR signaling causes intestinal hypomotility and impaired nutrient absorption, which gradually deplete internal nutrient stores and reduce organismal lifespan. Conversely, increased Capa/CapaR activity increases fluid and waste excretion. Furthermore, Capa/CapaR inhibits the release of glucagon-like adipokinetic hormone from the corpora cardiaca, which restricts energy mobilization from adipose tissue to avoid harmful hyperglycemia. Our results suggest that the Capa/CapaR circuit occupies a central node in a homeostatic program that facilitates the digestion and absorption of nutrients and regulates systemic energy balance.

scholarly journals The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress

2020 ◽  
Author(s):  
Olga Kubrak ◽  
Line Jensen ◽  
Nadja Ahrentløv ◽  
Takashi Koyama ◽  
Alina Malita ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Somatostatin Receptors ◽  
Gut Hormones ◽  
Peptide Hormone ◽  
Nutrient Stress ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Energy Mobilization ◽  
Gut Hormone

AbstractThe intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of the Drosophila gut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC). Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gut AstC or its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

scholarly journals The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress

2021 ◽  
Author(s):  
Olga Kubrak ◽  
Line Jensen ◽  
Nadja Ahrentloev ◽  
Takashi Koyama ◽  
Alina Malita ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Somatostatin Receptors ◽  
Gut Hormones ◽  
Peptide Hormone ◽  
Nutrient Stress ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Energy Mobilization ◽  
Gut Hormone

Abstract The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of the Drosophila gut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC), a Drosophila Somatostatin homolog. Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gut AstC or its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

Abstract 14: Central Nervous System Deletion of the Bbs1 Gene Causes Obesity and Hypertension in Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Deng-Fu Guo ◽  
Donald A Morgan ◽  
Charles C Searby ◽  
Darryl Y Nishmura ◽  
Val C Sheffield ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Arterial Pressure ◽  
Energy Homeostasis ◽  
Autosomal Recessive Disorder ◽  
Conditional Knockout ◽  
Peripheral Tissues ◽  
Knock Out ◽  
Obesity Phenotype

Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder with several features including obesity and hypertension. Systemic knock-out mouse models lacking expression of Bbs2, Bbs4 and Bbs6 genes, and Bbs1 M390R knock-in recapitulated many of the BBS phenotypes including obesity. However, the role and contribution of different tissues to the various phenotypes associated with BBS including obesity and hypertension remains unclear. To address this, we generated a new conditional knockout mouse where exon 3 of the Bbs1 gene is floxed. Cre-mediated recombination causes a frame shift resulting in a premature stop. We assessed whether deletion of the Bbs1 gene in the central nervous system (CNS) affects body weight and arterial pressure. Breeding Bbs1 flox with nestin Cre mice created mice deficient in Bbs1 gene only in the CNS as indicated by the loss of Bbs1 gene expression (by RT-PCR) in the hypothalamus, hippocampus, cortex and brainstem, but not in peripheral tissues such as adipose tissue, liver, kidney and skeletal muscle. Importantly, Bbs1 flox /nestin Cre mice display an obesity phenotype as indicated by the increased (P<0.05) body weight (40±1 g vs. 31±1 g in controls) and fat mass measured by MRI (23±2 g vs. 9±1 g in controls) in 25 weeks old mice. We found that the obesity phenotype in Bbs1 flox /nestin Cre mice is due to both an increase (P<0.05) in food intake (4.0±0.2 g vs. 3.1±0.3 g in controls) and reduction in energy expenditure as indicated by the decreased (P<0.05) O 2 consumption (2.8±0.3 mL/100g/min vs. 3.2±0.2 mL/100g/min in controls) and heat production (8.3±0.8 kcal/kg/h vs. 9.4±0.7 kcal/kg/h in controls). These results indicate that hyperphagia and low metabolic rate explain the development of obesity in Bbs1 flox /nestin Cre mice. Finally, we assessed by radiotelemetry the consequence on arterial pressure of ablating the Bbs1 gene throughout the CNS. Interestingly, CNS deletion of the Bbs1 gene recapitulates the hypertension phenotype of BBS as indicated by the elevated mean arterial pressure in Bbs1 flox /nestin Cre (123±3 mmHg) relative to littermate controls (112±4 mmHg, P=0.02). These findings demonstrate that Bbs genes in the CNS are critical for energy homeostasis and arterial pressure regulation.

scholarly journals Sex differences in the effects of androgens acting in the central nervous system on metabolism

2016 ◽  
Vol 18 (4) ◽  
pp. 415-424 ◽  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Central Nervous System ◽  
Nervous System ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Sexually Dimorphic ◽  
Metabolic Homeostasis ◽  
The Central Nervous System

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor.

scholarly journals Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes

2021 ◽  
Vol 22 (4) ◽  
pp. 1587
Author(s):  
Nuri Song ◽  
Da Yeon Jeong ◽  
Thai Hien Tu ◽  
Byong Seo Park ◽  
Hye Rim Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Nutrient Availability ◽  
Acid Oxidation ◽  
Cell Type ◽  
Metabolic Processes ◽  
Nutrient Metabolism ◽  
Peripheral Tissues ◽  
The Central Nervous System

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.

scholarly journals Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons

2008 ◽  
Vol 200 (1) ◽  
pp. 93-105 ◽  
Author(s):  
E Guillod-Maximin ◽  
A F Roy ◽  
C M Vacher ◽  
A Aubourg ◽  
V Bailleux ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Energy Homeostasis ◽  
Fluorescent Protein ◽  
Peripheral Tissues ◽  
Rat Hypothalamus ◽  
Ampk Phosphorylation ◽  
Hypothalamic Nuclei ◽  
Green Fluorescent ◽  
Amp Activated Protein Kinase

Adiponectin is involved in the control of energy homeostasis in peripheral tissues through Adipor1 and Adipor2 receptors. An increasing amount of evidence suggests that this adipocyte-secreted hormone may also act at the hypothalamic level to control energy homeostasis. In the present study, we observed the gene and protein expressions of Adipor1 and Adipor2 in rat hypothalamus using different approaches. By immunohistochemistry, Adipor1 expression was ubiquitous in the rat brain. By contrast, Adipor2 expression was more limited to specific brain areas such as hypothalamus, cortex, and hippocampus. In arcuate and paraventricular hypothalamic nuclei, Adipor1, and Adipor2 were expressed by neurons and astrocytes. Furthermore, using transgenic green fluorescent protein mice, we showed that Adipor1 and Adipor2 were present in pro–opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus. Finally, adiponectin treatment by intracerebroventricular injection induced AMP-activated protein kinase (AMPK) phosphorylation in the rat hypothalamus. This was confirmed byin vitrostudies using hypothalamic membrane fractions. In conclusion, Adipor1 and Adipor2 are both expressed by neurons (including POMC and NPY neurons) and astrocytes in the rat hypothalamic nuclei. Adiponectin is able to increase AMPK phosphorylation in the rat hypothalamus. These data reinforced a potential role of adiponectin and its hypothalamic receptors in the control of energy homeostasis.

scholarly journals Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission

2001 ◽  
Vol 82 (10) ◽  
pp. 2319-2326 ◽  
Author(s):  
J. D. Foster ◽  
D. W. Parnham ◽  
N. Hunter ◽  
M. Bruce
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Infection ◽  
Oral Route ◽  
Similar Distribution ◽  
Peripheral Tissues ◽  
Oral Transmission ◽  
Wide Range ◽  
Direct Contrast ◽  
The Central Nervous System

This study has examined the distribution of PrPSc in sheep by immunocytochemistry of tissues recovered from terminally affected animals following their experimental infection by the oral route with BSE. Despite a wide range of incubation period lengths, affected sheep showed a similar distribution of high levels of PrPSc throughout the central nervous system. PrPSc was also found in the lymphoid system, including parts of the digestive tract, and some components of the peripheral nervous system. These abundant PrPSc deposits in sheep in regions outside the central nervous system are in direct contrast with cattle infected with BSE, which show barely detectable levels of PrPSc in peripheral tissues. A number of genetically susceptible, challenged animals appear to have survived.

scholarly journals Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183605 ◽  
Author(s):  
Sirisha R. Kudumala ◽  
Tyrone Penserga ◽  
Jana Börner ◽  
Olesya Slipchuk ◽  
Priyanka Kakad ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrograde Transport ◽  
Adult Drosophila

Adipokinetic hormone stimulates neurones in the insect central nervous system.

1995 ◽  
Vol 198 (6) ◽  
pp. 1307-1311
Author(s):  
J J Milde ◽  
R Ziegler ◽  
M Wallstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Manduca Sexta ◽  
Central Action ◽  
Adipokinetic Hormone ◽  
Metabolic Functions ◽  
Simple Preparation ◽  
Pressure Injection ◽  
The Central Nervous System ◽  
Insect Central Nervous System

A simple preparation designed to screen and compare the central action of putative neuroactive agents in the moth Manduca sexta is described. This approach combines microinjections into the central nervous system with myograms recorded from a pair of spontaneously active mesothoracic muscles. Pressure injection of either octopamine or Manduca adipokinetic hormone (M-AKH) into the mesothoracic neuropile increases the monitored motor activity. Under the conditions used, the excitatory effects of M-AKH exceed those of the potent neuromodulator octopamine. This suggests that M-AKH plays a role in the central nervous system in addition to its known metabolic functions and supports recent evidence that neuropeptides in insects can be multifunctional.

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