scholarly journals Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior

2021 ◽  
Author(s):  
Kevin P Kelly ◽  
Mroj Alassaf ◽  
Camille E Sullivan ◽  
Ava E Brent ◽  
Zachary H Goldberg ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Prolonged Exposure ◽  
Genetic Model ◽  
Fat Body ◽  
Nutrient Status ◽  
Fruit Fly ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Insulin Resistant ◽  
Feeding Motivation

Diet-induced obesity (DIO) leads to dysfunctional feeding behavior. But the precise molecular nodes that are dysregulated by DIO that alter satiety sensing and feeding motivation are not fully disentangled. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation to mammalian nutrient sensing and energy balance. Using a longitudinal high sugar regime, in Drosophila, we sought to address how lipid alteration in fat cells alters feeding motivation. We find that long-term exposure to an HSD increases baseline feeding in flies. However, prolonged exposure to HSD degrades the hunger-driven feeding (HDF) response. Lipidomics analysis reveals that longitudinal exposure to HSD significantly alters whole body phospholipid profiles. Then, performing a systematic screen for phospholipid enzymes, we identify that a specific enzyme PECT, a rate-limiting enzyme in the phosphatidylethanolamine (PE) biosynthesis pathway and the fly ortholog of human PCYT2, was critical to maintaining hunger-driven feeding motivation. We show that disrupting PECT only in the fat body causes insulin-resistant phenotypes and a loss of hunger-driven feeding. Excitingly, we find that overexpression of PECT restores HSD-induced loss of hunger-driven feeding response. Strikingly human studies have noted a correlation between PCYT2/PECT levels and clinical obesity. Now, our unbiased studies in Drosophila provide specific genetic evidence for PECT in maintaining nutrient sensing during DIO. Our study provides novel insights on the role of phospholipids in interorgan communication of nutrient status.

scholarly journals Adipose mitochondrial metabolism controls body growth by modulating cytokine and insulin signaling

2021 ◽  
Author(s):  
Shrivani Sriskanthadevan-Pirahas ◽  
Michael J Turingan ◽  
Joel S Chahal ◽  
Erin Thorson ◽  
Savraj Grewal
Keyword(s):  
Nutrient Availability ◽  
Insulin Signaling ◽  
Fat Body ◽  
Nutrient Sensing ◽  
Body Growth ◽  
Mitochondrial Metabolism ◽  
Whole Body ◽  
Mitochondrial Morphology ◽  
Dietary Nutrients ◽  
Drosophila Larvae

Animals need to adapt their growth to fluctuations in nutrient availability to ensure proper development and survival. These adaptations often rely on specific nutrient-sensing tissues and their control of whole-body physiology through inter-organ communication. While the signaling mechanisms that underlie this communication are well studied, the contributions of metabolic alterations in the nutrient-sensing tissues are less clear. Here, we show how reprogramming of adipose mitochondrial metabolism controls whole-body growth in Drosophila larvae. We find that dietary nutrients alter fat body mitochondrial morphology to lower their bioenergetic activity, which we see can rewire fat body glucose metabolism. Strikingly, we find that genetic reduction of mitochondrial bioenergetics just in the fat body is sufficient to accelerate body growth and development. These growth effects are caused by inhibition of the fat-derived adipokine, TNFα/Eiger, which leads to enhanced systemic insulin signaling, the main hormonal stimulator of body growth. Our work reveals how reprogramming of mitochondrial metabolism in one nutrient-sensing tissue is able to couple whole body growth to nutrient availability.

Whole body withdrawal circuit and its involvement in the behavioral hierarchy of the mollusk Clione limacina

1996 ◽  
Vol 75 (2) ◽  
pp. 529-537 ◽  
Author(s):  
T. P. Norekian ◽  
R. A. Satterlie
Keyword(s):  
Feeding Behavior ◽  
Motor Neurons ◽  
Prey Capture ◽  
The Body ◽  
Whole Body ◽  
High Threshold ◽  
Behavioral Repertoire ◽  
Withdrawal Behavior ◽  
Cerebral Neurons ◽  
Clione Limacina

1. The behavioral repertoire of the holoplanktonic pteropod mollusk Clione limacina includes a few well-defined behaviors organized in a priority sequence. Whole body withdrawal takes precedence over slow swimming behavior, whereas feeding behavior is dominant over withdrawal. In this study a group of neurons is described in the pleural ganglia, which controls whole body withdrawal behavior in Clione. Each pleural withdrawal (Pl-W) neuron has a high threshold for spike generation and is capable of inducing whole body withdrawal in a semi-intact preparation: retraction of the body-tail, wings, and head. Each Pl-W neuron projects axons into the main central nerves and innervates all major regions of the body. 2. Stimulation of Pl-W neurons produces inhibitory inputs to swim motor neurons that terminate swimming activity in the preparation. In turn, Pl-W neurons receive inhibitory inputs from the cerebral neurons involved in the control of feeding behavior in Clione, neurons underlying extrusion of specialized prey capture appendages. Thus it appears that specific inhibitory connections between motor centers can explain the dominance of withdrawal behavior over slow swimming and feeding over withdrawal in Clione.

Whole body extract of Mediterranean fruit fly males elicits high attraction in virgin females

2008 ◽  
Vol 127 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Vassilis G. Mavraganis ◽  
Constandinos Liaropoulos ◽  
Nikos T. Papadopoulos ◽  
Nikos A. Kouloussis ◽  
Theodoros Broumas
Keyword(s):  
Fruit Fly ◽  
Mediterranean Fruit Fly ◽  
Whole Body ◽  
Body Extract ◽  
High Attraction

Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

2014 ◽  
Vol 307 (10) ◽  
pp. E885-E895 ◽  
Author(s):  
Marjolein A. Wijngaarden ◽  
Leontine E. H. Bakker ◽  
Gerard C. van der Zon ◽  
Peter A. C. 't Hoen ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Lipid Oxidation ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Protein Kinase Activity ◽  
Short Term ◽  
Muscle Energy

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

Central and Peripheral Clock Control of Circadian Feeding Rhythms

2021 ◽  
pp. 074873042110458
Author(s):  
Carson V. Fulgham ◽  
Austin P. Dreyer ◽  
Anita Nasseri ◽  
Asia N. Miller ◽  
Jacob Love ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Feeding Behavior ◽  
Molecular Clock ◽  
Fat Body ◽  
Molecular Clocks ◽  
Central Brain ◽  
Feeding Rhythms ◽  
Free Running ◽  
The Brain

Many behaviors exhibit ~24-h oscillations under control of an endogenous circadian timing system that tracks time of day via a molecular circadian clock. In the fruit fly, Drosophila melanogaster, most circadian research has focused on the generation of locomotor activity rhythms, but a fundamental question is how the circadian clock orchestrates multiple distinct behavioral outputs. Here, we have investigated the cells and circuits mediating circadian control of feeding behavior. Using an array of genetic tools, we show that, as is the case for locomotor activity rhythms, the presence of feeding rhythms requires molecular clock function in the ventrolateral clock neurons of the central brain. We further demonstrate that the speed of molecular clock oscillations in these neurons dictates the free-running period length of feeding rhythms. In contrast to the effects observed with central clock cell manipulations, we show that genetic abrogation of the molecular clock in the fat body, a peripheral metabolic tissue, is without effect on feeding behavior. Interestingly, we find that molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions, likely due to a long endogenous period of the fat body clock. Under these conditions, the period of feeding rhythms tracks with molecular oscillations in central brain clock cells, consistent with a primary role of the brain clock in dictating the timing of feeding behavior. Finally, despite a lack of effect of fat body selective manipulations, we find that flies with simultaneous disruption of molecular clocks in multiple peripheral tissues (but with intact central clocks) exhibit decreased feeding rhythm strength and reduced overall food intake. We conclude that both central and peripheral clocks contribute to the regulation of feeding rhythms, with a particularly dominant, pacemaker role for specific populations of central brain clock cells.

scholarly journals Effects of photoperiod on daily locomotor activity, energy expenditure, and feeding behavior in a seasonal mammal

2010 ◽  
Vol 298 (5) ◽  
pp. R1409-R1416 ◽  
Author(s):  
Amy Warner ◽  
Preeti H. Jethwa ◽  
Catherine A. Wyse ◽  
Helen I'Anson ◽  
John M. Brameld ◽  
...  
Keyword(s):  
Body Weight ◽  
Locomotor Activity ◽  
Energy Expenditure ◽  
Feeding Behavior ◽  
Heat Production ◽  
Prolonged Exposure ◽  
Dark Phase ◽  
Daily Rhythms ◽  
Dark Cycle ◽  
Activity Energy

The objective of this study was to determine whether the previously observed effects of photoperiod on body weight in Siberian hamsters were due to changes in the daily patterns of locomotor activity, energy expenditure, and/or feeding behavior. Adult males were monitored through a seasonal cycle using an automated comprehensive laboratory animal monitoring system (CLAMS). Exposure to a short-day photoperiod (SD; 8:16-h light-dark cycle) induced a significant decline in body weight, and oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and heat production all decreased reaching a nadir by 16 wk of SD. Clear daily rhythms in locomotor activity, V̇o2, and V̇co2 were observed at the start of the study, but these all progressively diminished after prolonged exposure to SD. Rhythms in feeding behavior were also detected initially, reflecting an increase in meal frequency but not duration during the dark phase. This rhythm was lost by 8 wk of SD exposure such that food intake was relatively constant across dark and light phases. After 18 wk in SD, hamsters were transferred to a long-day photoperiod (LD; 16:8-h light-dark cycle), which induced significant weight gain. This was associated with an increase in energy intake within 2 wk, while V̇o2, V̇co2, and heat production all increased back to basal levels. Rhythmicity was reestablished within 4 wk of reexposure to long days. These results demonstrate that photoperiod impacts on body weight via complex changes in locomotor activity, energy expenditure, and feeding behavior, with a striking loss of daily rhythms during SD exposure.

Effects of a unique conjugate of α-lipoic acid and γ-linolenic acid on insulin action in obese Zucker rats

2000 ◽  
Vol 278 (2) ◽  
pp. R453-R459 ◽  
Author(s):  
J. Anthony Peth ◽  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Hans J. Tritschler ◽  
Erik J. Henriksen
Keyword(s):  
Fatty Acid ◽  
Essential Fatty Acid ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Additive Effects ◽  
Insulin Resistant ◽  
Obese Zucker Rats

The purpose of this study was to assess the individual and interactive effects of the antioxidant α-lipoic acid (LPA) and the n-6 essential fatty acid γ-linolenic acid (GLA) on insulin action in insulin-resistant obese Zucker rats. LPA, GLA, and a unique conjugate consisting of equimolar parts of LPA and GLA (LPA-GLA) were administered for 14 days at 10, 30, or 50 mg ⋅ kg body wt− 1 ⋅ day− 1. Whereas LPA was without effect at 10 mg/kg, at 30 and 50 mg/kg it elicited 23% reductions ( P < 0.05) in the glucose-insulin index (the product of glucose and insulin areas under the curve during an oral glucose tolerance test and an index of peripheral insulin action) that were associated with significant increases in insulin-mediated (2 mU/ml) glucose transport activity in isolated epitrochlearis (63–65%) and soleus (33–41%) muscles. GLA at 10 and 30 mg/kg caused 21–25% reductions in the glucose-insulin index and 23–35% improvements in insulin-mediated glucose transport in epitrochlearis muscle. The beneficial effects of GLA disappeared at 50 mg/kg. At 10 and 30 mg/kg, the LPA-GLA conjugate elicited 29 and 38% reductions in the glucose-insulin index. These LPA-GLA-induced improvements in whole body insulin action were accompanied by 28–63 and 38–57% increases in insulin-mediated glucose transport in epitrochlearis and soleus muscles and resulted from the additive effects of LPA and GLA. At 50 mg/kg, the metabolic improvements due to LPA-GLA were substantially reduced. In summary, these results indicate that the conjugate of the antioxidant LPA and the n-6 essential fatty acid GLA elicits significant dose-dependent improvements in whole body and skeletal muscle insulin action on glucose disposal in insulin-resistant obese Zucker rats. Moreover, these actions of LPA-GLA are due to the additive effects of its individual components.

scholarly journals PPA1 Regulates Systemic Insulin Sensitivity by Maintaining Adipocyte Mitochondria Function as a Novel PPARγ Target Gene

2021 ◽  
Author(s):  
Ye Yin ◽  
Yangyang Wu ◽  
Xu Zhang ◽  
Yeting Zhu ◽  
Yue Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Metabolic Disorders ◽  
Target Gene ◽  
Fat Body ◽  
Whole Body ◽  
Inorganic Pyrophosphatase ◽  
Severe Insulin Resistance ◽  
Adipose Tissue Development ◽  
First Time

<a>Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development of obesity-associated metabolic disorders. Inorganic Pyrophosphatase 1 (PPA1) is an enzyme catalyzes the hydrolysis of PPi to Pi, and is required for anabolism to take place in cells. Although alternation of PPA1 has been related to some diseases, the importance of PPA1 in metabolic syndromes has never been discussed before. In this study, we found that global PPA1 knockout mice (PPA1<sup>+/-</sup>) showed impaired glucose tolerance and severe insulin resistance under HFD feeding. In addition, impaired adipose tissue development and ectopic lipid accumulation were also observed. Conversely, overexpression of PPA1 in adipose tissue by AAV injection can partly reverse the metabolic disorders in PPA1<sup>+/-</sup> mice, suggesting that impaired adipose tissue function is responsible for the metabolic disorders observed in PPA1<sup>+/- </sup>mice. Mechanistic studies revealed that PPA1 acted as a PPARγ target gene to maintain mitochondrial function in adipocytes. Furthermore, specific knockdown of PPA1 in fat body of <i>Drosophila</i> led to impaired mitochondria morphology, decreased lipid storage, and made <i>Drosophila</i> more sensitive to starvation. In conclusion, for the first time, our findings demonstrated the importance of PPA1 in maintaining adipose tissue function and whole body metabolic homeostasis.</a>

scholarly journals Hepatokine ERAP1 impairs skeletal muscle insulin sensitivity via ADRB2/PKA pathway

2020 ◽  
Author(s):  
Feifan Guo ◽  
Yuguo Niu ◽  
Haizhou Jiang ◽  
Hanrui Yin ◽  
Fenfen Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Neutralizing Antibodies ◽  
Leptin Receptor ◽  
Whole Body ◽  
C2c12 Myotubes ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Sensitivity ◽  
Pka Pathway

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.

scholarly journals Non-canonical function of theSex-lethalgene controls the protogyny phenotype inDrosophila melanogaster

2021 ◽  
Author(s):  
Ki-Hyeon Seong ◽  
Siu Kang
Keyword(s):  
Dosage Compensation ◽  
Sexual Maturation ◽  
Fruit Fly ◽  
Fruit Flies ◽  
Activity Monitoring ◽  
Whole Body ◽  
Human Beings ◽  
Canonical Function ◽  
Individual Activity ◽  
Time Points

AbstractMany animal species exhibit sex differences in the time period prior to reaching sexual maturity. However, the underlying mechanism for such biased maturation remains poorly understood. Females of the fruit flyDrosophila melanogastereclose 4 h faster on average than males, owing to differences in the pupal period between the sexes; this characteristic is referred to as the protogyny phenotype. Here, we aimed to elucidate the mechanism underlying the protogyny phenotype in the fruit fly using our newly developedDrosophilaIndividual Activity Monitoring and Detecting System (DIAMonDS), which can continuously detect the precise timing of both pupariation and eclosion of individual flies. Via this system, following the laying of eggs, we detected the precise time points of pupariation and eclosion of a large number of individual flies simultaneously and succeeded in identifying the tiny differences in pupal duration between females and males. We first explored the role of physiological sex by establishing transgender flies via knockdown of the sex-determination gene,transformer(tra) and its co-factortra2, which retained the protogyny phenotype. In addition, disruption of dosage compensation bymale-specific lethal(msl-2) knockdown did not affect the protogyny phenotype. TheDrosophilamaster sex switch gene—Sxlpromotes female differentiation viatraand turns off male dosage compensation through the repression ofmsl-2.However, we observed that stage-specific whole-body knockdown and mutation ofSxlinduced disturbance of the protogyny phenotype. These results suggest that an additional, non-canonical function ofSxlinvolves establishing the protogyny phenotype inD. melanogaster.Author summaryA wide variety of animals show differences in time points of sexual maturation between sexes. For example, in many mammals, including human beings, females mature faster than males. This maturation often takes several months or years, and precisely detecting the time point of maturation is challenging, because of the continuity of growth, especially in mammals. Moreover, the reason behind the difference in sexual maturation time points between sexes is not fully understood. The fruit flyDrosophila—a model organism—also shows biased maturation between the sexes, with females emerging 4 h faster than males (a characteristic known as the protogyny phenotype). To understand the mechanism underlying the protogyny phenotype, we used our newly developed system,DrosophilaIndividual Activity Monitoring and Detecting System (DIAMonDS), to detect the precise eclosion point in individual fruit flies. Surprisingly, our analysis of transgender flies obtained by knockdown and overexpression techniques indicated that a physiological gender might not be necessary requirement for protogyny and that a non-canonical novel function of the fruit fly master sex switch gene,Sxl, regulates protogyny in fruit flies.

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