Regulation of lipid droplet homeostasis by hypoxia inducible lipid droplet associated HILPDA

Rodriguez, Montserrat A. de la Rosa; Kersten, Sander

doi:10.1016/j.bbalip.2020.158738

Cited by 34 publications

(36 citation statements)

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“…expansion). HILPDA has been shown to co-localize with the lipogenic enzymes DGAT1 and DGAT2 [ 11 ], which were both identified as DEGs in our study (Table 2 ). DGATs catalyze the final rate-limiting step in the formation of triglycerides.…”

Section: Discussionmentioning

confidence: 56%

“…DGATs catalyze the final rate-limiting step in the formation of triglycerides. In line with this, HILPDA has been shown to promote intracellular lipid accumulation by enhancing triglyceride synthesis [ 11 ]. Overexpression of HILPDA, but not DGAT1/2, is associated with shorter overall survival in pancreatic cancer patients (Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Sixty-five factors were identified as lipid droplet-associated factors by literature search and analysis. Factor name References Factor name References Factor name References ABHD5 (CGI-58) [ 11 , 12 , 15 , 17 – 20 , 22 – 29 , 34 , 35 , 37 , 38 ] ACAT1 [ 28 , 33 ] ACSL3 [ 14 , 15 , 18 , 35 ] ACSL4 [ 18 , 35 ] AGPAT2 (BSCL1) [ 18 , 21 ] ANGPTL8 (C19orf80) [ 21 ] APOA4 [ 18 ] APOB [ 18 ] AUP1 [ 15 , 18 ] BSCL2 (Seipin) [ 14 , 18 , 20 ] CAV1 (BSCL3) [ 18 , 20 , 29 ] CAV2 [ 18 , 29 ] CAVIN1 [ 18 ] CES1 [ 18 , 32 ] CIDEA …”

Section: Resultsmentioning

confidence: 99%

“…3 a), suggesting that additional roles of HILPDA, other than regulating triacylglyceride (TAG) synthesis, may influence the outcome of pancreatic cancer patients. Indeed, HILPDA inhibits the rate-limiting enzyme of TAG hydrolysis PNPLA2 (ATGL), leading to inhibition of lipolysis, attenuated fatty acid oxidation and ROS production [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…There was no restriction on the publication period. We analyzed all retrieved articles [ 11 – 39 ], and selected factors that were described to localize on lipid droplet including factors on contact sites to other organelles, such as endoplasmic reticulum and mitochondria.…”

Section: Methodsmentioning

confidence: 99%

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Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis

et al. 2021

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Background Pancreatic cancer is the fourth leading cause of cancer deaths in the United States both in females and in males, and is projected to become the second deadliest cancer by 2030. The overall 5-year survival rate remains at around 10%. Cancer metabolism and specifically lipid metabolism plays an important role in pancreatic cancer progression and metastasis. Lipid droplets can not only store and transfer lipids, but also act as molecular messengers, and signaling factors. As lipid droplets are implicated in reprogramming tumor cell metabolism and in invasion and migration of pancreatic cancer cells, we aimed to identify lipid droplet-associated genes as prognostic markers in pancreatic cancer. Methods We performed a literature search on review articles related to lipid droplet-associated proteins. To select relevant lipid droplet-associated factors, bioinformatics analysis on the GEPIA platform (data are publicly available) was carried out for selected genes to identify differential expression in pancreatic cancer versus healthy pancreatic tissues. Differentially expressed genes were further analyzed regarding overall survival of pancreatic cancer patients. Results 65 factors were identified as lipid droplet-associated factors. Bioinformatics analysis of 179 pancreatic cancer samples and 171 normal pancreatic tissue samples on the GEPIA platform identified 39 deferentially expressed genes in pancreatic cancer with 36 up-regulated genes (ACSL3, ACSL4, AGPAT2, BSCL2, CAV1, CAV2, CAVIN1, CES1, CIDEC, DGAT1, DGAT2, FAF2, G0S2, HILPDA, HSD17B11, ICE2, LDAH, LIPE, LPCAT1, LPCAT2, LPIN1, MGLL, NAPA, NCEH1, PCYT1A, PLIN2, PLIN3, RAB5A, RAB7A, RAB8A, RAB18, SNAP23, SQLE, VAPA, VCP, VMP1) and 3 down-regulated genes (FITM1, PLIN4, PLIN5). Among 39 differentially expressed factors, seven up-regulated genes (CAV2, CIDEC, HILPDA, HSD17B11, NCEH1, RAB5A, and SQLE) and two down-regulation genes (BSCL2 and FITM1) were significantly associated with overall survival of pancreatic cancer patients. Multivariate Cox regression analysis identified CAV2 as the only independent prognostic factor. Conclusions Through bioinformatics analysis, we identified nine prognostic relevant differentially expressed genes highlighting the role of lipid droplet-associated factors in pancreatic cancer.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis

et al. 2021

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Association of Birth Asphyxia With Regional White Matter Abnormalities Among Patients With Schizophrenia and Bipolar Disorders

et al. 2021

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IMPORTANCE White matter (WM) abnormalities are commonly reported in psychiatric disorders.Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear.OBJECTIVE To examine the association between birth asphyxia and WM in adult patients with schizophrenia and bipolar disorders (BDs) compared with healthy adults. DESIGN, SETTING, AND PARTICIPANTSIn this case-control study, all individuals participating in the ongoing Thematically Organized Psychosis project were linked to the Medical Birth Registry of Norway (MBRN), where a subset of 271 patients (case group) and 529 healthy individuals (control group) had undergone diffusion-weighted imaging (DWI). Statistical analyses were performed from June 16, 2020, to March 9, 2021.EXPOSURES Birth asphyxia was defined based on measures from standardized reporting at birth in the MBRN. MAIN OUTCOMES AND MEASURES Associations between birth asphyxia and WM regions ofinterest diffusion metrics, ie, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), were compared between groups using analysis of covariance, adjusted for age, age squared, and sex. RESULTSOf the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [SD] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years). Birth asphyxia measures were identified in 15% to 16% of participants, independent of group. The posterior limb of the internal capsule (PLIC) showed a significant diagnostic group × birth asphyxia interaction (F (1, 843) = 11.46; P = .001), reflecting a stronger association between birth asphyxia and FA in the case group than the control group. RD, but not AD, also displayed a significant diagnostic group × birth asphyxia interaction (F (1, 843) = 9.28; P = .002) in the PLIC, with higher values in patients with birth asphyxia and similar effect sizes as observed for FA. CONCLUSIONS AND RELEVANCEIn this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development. Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important WM brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and BDs.

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Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia‐reperfusion of transplanted grafts

Kamińska,

Skrzycki

2024

Cell Biology International

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Ischemia‐reperfusion injury is an event concerning any organ under a procedure of transplantation. The early result of ischemia is hypoxia, which causes malfunction of mitochondria and decrease in cellular ATP. This leads to disruption of cellular metabolism. Reperfusion also results in cell damage due to reoxygenation and increased production of reactive oxygen species, and later by induced inflammation. In damaged and hypoxic cells, the endoplasmic reticulum (ER) stress pathway is activated by increased amount of damaged or misfolded proteins, accumulation of free fatty acids and other lipids due to inability of their oxidation (lipotoxicity). ER stress is an adaptive response and a survival pathway, however, its prolonged activity eventually lead to induction of apoptosis. Sustaining cell functionality in stress conditions is a great challenge for transplant surgeons as it is crucial for maintaining a desired level of graft vitality. Pathways counteracting negative consequences of ischemia‐reperfusion are autophagy and lipid droplets (LD) metabolism. Autophagy remove damaged organelles and molecules driving them to lysosomes, digested simpler compounds are energy source for the cell. Mitophagy and ER‐phagy results in improvement of cell energetic balance and alleviation of ER stress. This is important in sustaining metabolic homeostasis and thus cell survival. LD metabolism is connected with autophagy as LD are degraded by lipophagy, a source of free fatty acids and glycerol—thus autophagy and LD can readily remove lipotoxic compounds in the cell. In conclusion, monitoring and pharmaceutic regulation of those pathways during transplantation procedure might result in increased/improved vitality of transplanted organ.

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Regulation of lipid droplet homeostasis by hypoxia inducible lipid droplet associated HILPDA

Cited by 34 publications

References 34 publications

Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis

Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis

Association of Birth Asphyxia With Regional White Matter Abnormalities Among Patients With Schizophrenia and Bipolar Disorders

Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia‐reperfusion of transplanted grafts

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