Minicocci I

References (3)

Title : The Fibrinogen-like Domain of ANGPTL3 Facilitates Lipolysis in 3T3-L1 Cells by Activating the Intracellular Erk Pathway - Bini_2022_Biomolecules_12_
Author(s) : Bini S , Pecce V , Di Costanzo A , Polito L , Ghadiri A , Minicocci I , Tambaro F , Covino S , Arca M , D'Erasmo L
Ref : Biomolecules , 12 : , 2022
Abstract : BACKGROUND: ANGPTL3 stimulates lipolysis in adipocytes, but the underlying molecular mechanism is yet unknown. The C-terminal fibrinogen-like domain of ANGPTL3 (ANGPTL3-Fld) activates the AKT pathway in endothelial cells. Hence, we evaluated whether ANGPTL3-Fld stimulates lipolysis in adipocytes through the MAPK kinase pathway. MATERIALS AND METHODS: 3T3-L1 adipocytes were treated with isoproterenol (ISO), ANGPTL3-Fld, or both. Lipolysis was evaluated through the release of free fatty acids (FFAs) in the culture medium. The activation status of intracellular kinases was evaluated with and without the inhibition of the BRAF-ERK arm of the MAPK pathway. RESULTS: ANGPTL3-Fld alone was not able to activate lipolysis, while the combination of ANGPTL3-Fld and ISO determined a 10-fold enrichment of the FFA concentration in the culture medium with an incremental effect (twofold) when compared with ISO alone. ANGPTL3-Fld alone inhibited hormone-sensitive lipase (HSL), whereas the treatment with ISO induced the activation of HSL. The net balance of ANGPTL3-Fld and ISO cotreatment resulted in HSL activation. The results indicate that ANGPTL3-Fld generated an intracellular activation signal involving the MAPK-ERK pathway, possibly through the PDGFRbeta-PLCgamma-AMPK axis. CONCLUSION: ANGPTL3-Fld appears to act as a facilitator of lipolysis in adipocytes, and this effect was driven by a signal mediated by a pathway that is different from the canonical beta-adrenergic stimulus.
ESTHER : Bini_2022_Biomolecules_12_
PubMedSearch : Bini_2022_Biomolecules_12_
PubMedID: 35454174

Title : Contribution of mutations in low density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) genes to familial combined hyperlipidemia (FCHL): A reappraisal by using a resequencing approach - Minicocci_2015_Atherosclerosis_242_618
Author(s) : Minicocci I , Prisco C , Montali A , Di Costanzo A , Ceci F , Pigna G , Arca M
Ref : Atherosclerosis , 242 :618 , 2015
Abstract : BACKGROUND: Defective low-density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) alleles have been implicated in familial combined hyperlipidemia (FCHL). However, their contribution might have been influenced by diagnostic criteria. This study was aimed to reassess the frequency of rare and common variants in LDLR and LPL in FCHL individuals classified with stringent criteria.
METHODS: LDLR and LPL were resequenced in 208 FHCL and 171 controls. Variants were classified as loss- (LOF) or gain-of-function (GOF) based upon in silico prediction, familial segregation and available functional data.
RESULTS: Eight LOF variants were detected in LDLR, 6 of which were missense and 2 were predicted to disrupt normal splicing; all were present at heterozygous state. They were found in 10 FCHL but not in controls, thus indicating that 4.8% of FCHL individuals should be reclassified as FH. LDL-C (positive) and BMI (negative) were the strongest predictors of LDLR mutations with LDL-C 181 mg/dl being the best threshold for diagnosing the presence of dysfunctional LDLR alleles. The cumulative prevalence of definite LPL defective alleles (1 rare and 2 common heterozygous missense variants) was comparable between FCHL and controls (10.1% vs. 10.5%). Conversely, the LPL GOF variant p.Ser474* showed a lower frequency in FCHL than in controls (13.5% vs. 24.0%, p = 0.008). Overall, LOF LPL variants did not show a TG-modulating effect.
CONCLUSIONS: Our findings indicate that, in well characterized FCHL individuals, variants in LDLR and LPL provide a small contribution to this dyslipidemia, thus limiting the need for such genetic testing.
ESTHER : Minicocci_2015_Atherosclerosis_242_618
PubMedSearch : Minicocci_2015_Atherosclerosis_242_618
PubMedID: 26342331

Title : Genetic variants in adipose triglyceride lipase influence lipid levels in familial combined hyperlipidemia - Nanni_2010_Atherosclerosis_213_206
Author(s) : Nanni L , Quagliarini F , Megiorni F , Montali A , Minicocci I , Campagna F , Pizzuti A , Arca M
Ref : Atherosclerosis , 213 :206 , 2010
Abstract : OBJECTIVE: Familial combined hyperlipidemia (FCHL) has been associated with abnormalities in fatty acid metabolism. The adipose triglyceride lipase (PNPLA2) plays a pivotal role in the turnover of fatty acids in adipose tissue and liver. This study was designed to evaluate whether selected PNPLA2 variants may influence the susceptibility to FCHL or its lipid-related traits. METHODS: Four SNPs within the PNPLA2 gene (rs7925131, rs7942159, rs66460720 and the nonsynonymous P481L) were selected based on previous association with decreased plasma levels of free fatty acids (FFA) and total triglycerides (TG) and their high frequency (MAF>0.25). These SNPs were genotyped in 214 FCHL individuals from 83 families and in 103 controls and the corresponding haplotypes were reconstructed. RESULTS: No association between individual SNPs and the FCHL trait was observed. However, two PNPLA2 haplotypes were associated with lower risk of FCHL (P<0.004 after Bonferroni's correction). Compared to the others, these haplotypes were related to lower TG (118.9 +/- 66.8 vs. 197.1 +/- 114.7 mg/dl; P=0.001) and higher HDL-C (62.3 +/- 15.8 vs. 51.0 +/- 15.0 mg/dl; P<0.005). In a subgroup of studied subjects (n=63) protective haplotypes were also associated with lower FFA levels (0.33 +/- 0.11 vs. 0.46 +/- 0.18 mEq/L; P<0.05). These effects were independent from age, BMI and HOMA(IR). CONCLUSION: These data demonstrate that variants within PNPLA2 may modulate the TG component of FCHL trait, thus implicating PNPLA2 as modifier gene in this lipid disorder. They also suggest a potential role of PNPLA2 in the metabolism of TG-rich lipoproteins.
ESTHER : Nanni_2010_Atherosclerosis_213_206
PubMedSearch : Nanni_2010_Atherosclerosis_213_206
PubMedID: 20832801