scholarly journals C. elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling

2017 ◽  
Author(s):  
JF Clark ◽  
M Meade ◽  
G Ranepura ◽  
DH Hall ◽  
C Savage-Dunn
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Bmp Signaling ◽  
Lipid Homeostasis ◽  
Metabolic Homeostasis ◽  
C Elegans ◽  
Lipid Droplet Size ◽  
Lipid Stores

AbstractMetabolic homeostasis is coordinately controlled by diverse inputs, which must be understood to combat metabolic disorders. Here we introduce DBL-1, the C. elegans BMP2/4 homolog, as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL 1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling (IIS) in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through inter-organ signaling to IIS, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.

scholarly journals Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection

2019 ◽  
Vol 116 (44) ◽  
pp. 22322-22330 ◽  
Author(s):  
James D. Nhan ◽  
Christian D. Turner ◽  
Sarah M. Anderson ◽  
Chia-An Yen ◽  
Hans M. Dalton ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Mapk Signaling ◽  
Host Responses ◽  
Lipid Homeostasis ◽  
Epigenetic Landscape ◽  
C Elegans ◽  
Metabolic Outcomes ◽  
Cellular Defenses ◽  
Pathogen Response ◽  
Lipid Stores

Early host responses toward pathogens are essential for defense against infection. In Caenorhabditis elegans, the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan. Here, we show that exposing C. elegans to Pseudomonas aeruginosa similarly drives the rapid depletion of somatic, but not germline, lipid stores. Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets, which alleviates negative metabolic outcomes. Similarly, exposure to oxidative stress redirects SKN-1 activity away from pathogen response genes while restoring somatic lipid distribution. In addition, activating p38/MAPK signaling in the absence of pathogens, is sufficient to drive SKN-1–dependent loss of somatic fat. These data define a SKN-1– and p38-dependent axis for coordinating pathogen responses, lipid homeostasis, and survival and identify transcriptional redirection, rather than inactivation, as a mechanism for counteracting the pleiotropic consequences of aberrant transcriptional activity.

scholarly journals Mechanism of Interaction of BMP and Insulin Signaling in C. elegans Development and Homeostasis

2019 ◽  
Author(s):  
James F. Clark ◽  
Emma J. Ciccarelli ◽  
Gehan Ranepura ◽  
Muhammad S. Hasan ◽  
Alicia Meléndez ◽  
...  
Keyword(s):  
Bmp Signaling ◽  
Lipid Homeostasis ◽  
Signaling Crosstalk ◽  
C Elegans ◽  
Morphogenetic Protein ◽  
Autophagy Induction ◽  
Dauer Formation ◽  
And Function ◽  
Modes Of Interaction ◽  
Molecular Components

AbstractA small number of peptide growth factor ligands are used repeatedly in development and homeostasis to drive programs of cell differentiation and function. Cells and tissues must integrate inputs from these diverse signals correctly, while failure to do so leads to pathology, reduced fitness, or death. Previous work using the nematode C. elegans identified an interaction between the bone morphogenetic protein (BMP) and insulin/IGF-1-like signaling (IIS) pathways in the regulation of lipid homeostasis. The molecular components required for this interaction, however, were not known. Here we report that INS-4, one of 40 insulin-like peptides (ILPs), is specifically regulated by BMP signaling to modulate fat accumulation. Furthermore, we find that the IIS transcription factor DAF-16/FoxO, but not SKN-1/Nrf, acts downstream of BMP signaling in lipid homeostasis. Interestingly, BMP activity alters sensitivity of these two transcription factors to IIS-promoted cytoplasmic retention in opposite ways. Finally, we probe the extent of BMP and IIS interactions by testing two additional IIS functions, dauer formation and autophagy induction. Coupled with our previous work and that of other groups, we conclude that BMP and IIS pathways have at least three modes of interaction: independent, epistatic, and antagonistic. The molecular interactions we identify provide new insight into mechanisms of signaling crosstalk and potential therapeutic targets for IIS-related pathologies such as diabetes and metabolic syndrome.

scholarly journals Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans

2020 ◽  
Author(s):  
Qinghua Zhou ◽  
Qin-Li Wan ◽  
Xiao Meng ◽  
Chongyang Wang ◽  
Wenyu Dai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Epigenetic Inheritance ◽  
Chromatin Modifications ◽  
C Elegans ◽  
Metabolic Genes ◽  
Epigenetic Signal ◽  
Histone H3k4 ◽  
Delta 9 Desaturase

Abstract As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents could affect progeny’s lipid accumulation through multi-generational epigenetic inheritance. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we established a model of C. elegans fed with a high fat diet (HFD) that led to obvious lipid accumulation, which can be propagated their progeny. Using this model, we discovered that transcription factors DAF-16/FOXO and SBP-1, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturase (fat-5, fat-6, and fat-7) are required for transgenerational fat accumulation. Additionally, histone H3K4 tri-methylation (H3K4me3) marks genes related to lipid metabolism and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes that a network of lipid metabolic genes and chromatin modifications work together to achieve multigenerational obesogenic effects.

scholarly journals Arabidopsis lipid droplet‐associated protein (LDAP) – interacting protein ( LDIP ) influences lipid droplet size and neutral lipid homeostasis in both leaves and seeds

2017 ◽  
Vol 92 (6) ◽  
pp. 1182-1201 ◽  
Author(s):  
Michal Pyc ◽  
Yingqi Cai ◽  
Satinder K. Gidda ◽  
Olga Yurchenko ◽  
Sunjung Park ◽  
...  
Keyword(s):  
Neutral Lipid ◽  
Droplet Size ◽  
Lipid Droplet ◽  
Lipid Homeostasis ◽  
Interacting Protein ◽  
Lipid Droplet Size

scholarly journals Lipid metabolism in Calanus finmarchicus is sensitive to variations in predation risk and food availability

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elise Skottene ◽  
Ann M. Tarrant ◽  
Dag Altin ◽  
Rolf Erik Olsen ◽  
Marvin Choquet ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Predation Risk ◽  
Food Availability ◽  
Lipid Accumulation ◽  
Developmental Stages ◽  
Life Stage ◽  
Calanus Finmarchicus ◽  
Expression Of Genes ◽  
Food Conditions ◽  
Lipid Stores

AbstractLate developmental stages of the marine copepods in the genus Calanus can spend extended periods in a dormant stage (diapause) that is preceded by the accumulation of large lipid stores. We assessed how lipid metabolism during development from the C4 stage to adult is altered in response to predation risk and varying food availability, to ultimately understand more of the metabolic processes during development in Calanus copepods. We used RNA sequencing to assess if perceived predation risk in combination with varied food availability affects expression of genes associated with lipid metabolism and diapause preparation in C. finmarchicus. The lipid metabolism response to predation risk differed depending on food availability, time and life stage. Predation risk caused upregulation of lipid catabolism with high food, and downregulation with low food. Under low food conditions, predation risk disrupted lipid accumulation. The copepods showed no clear signs of diapause preparation, supporting earlier observations of the importance of multiple environmental cues in inducing diapause in C. finmarchicus. This study demonstrates that lipid metabolism is a sensitive endpoint for the interacting environmental effects of predation pressure and food availability. As diapause may be controlled by lipid accumulation, our findings may contribute towards understanding processes that can ultimately influence diapause timing.

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

scholarly journals The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1078
Author(s):  
Debasish Roy ◽  
Andrea Tedeschi
Keyword(s):  
Nervous System ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Axon Regeneration ◽  
Axon Growth ◽  
The Body ◽  
Cns Repair ◽  
Cord Injury ◽  
Cns Trauma

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

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