Short-chain fatty acids levels in human milk are not affected by holder pasteurization and high hydrostatic pressure processing

Sterilized donor milk (DM) is frequently used for feeding preterm infants. To date, the effect of different modes of DM sterilization on short-chain fatty acids (SCFAs) remains unknown. We aimed to quantify SCFAs in DM samples after two types of milk sterilization: the Holder pasteurization (HoP) and a high hydrostatic pressure (HP) processing. Eight pooled DM samples were sterilized by HoP (62.5°C for 30 min) or processed by HP (350 MPa at 38°C). Raw DM was used as control. Six SCFAs were quantified by gas chromatography/mass spectrometry. Compared to raw milk, both HoP and HP treatment did not significantly modulate the concentration of acetate, butyrate, propionate and isovalerate in DM. Valerate and isobutyrate were undetectable in DM samples. In conclusion, both HoP and HP processing preserved milk SCFAs at their initial levels in raw human milk

Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals

We have established a pig resource population specifically designed to elucidate the genetics involved in development of obesity and obesity related co-morbidities by crossing the obesity prone Göttingen Minipig breed with two lean production pig breeds. In this study we have performed genome wide association (GWA) to identify loci with effect on blood lipid levels. The most significantly associated single nucleotide polymorphisms (SNPs) were used for linkage disequilibrium (LD) and haplotype analyses. Three separate haploblocks which influence the ratio between high density lipoprotein cholesterol and total cholesterol (HDL-C/CT), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels respectively were identified on Sus Scrofa chromosome 3 (SSC3). Large additive genetic effects were found for the HDL-C/CT and LDL-C haplotypes. Haplotypes segregating from Göttingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Göttingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload

Abstract Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex-and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93 %, P < 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n = 7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n = 11) (−58 % and −73 %, respectively, P < 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43 + − 5; non-C282Y: 25 + − 8; controls: 32 + − 7 %; P < 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23 + − 5; non-C282Y: 39 + − 10; controls: 26 + − 4 %; P < 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal

Immuno-inflammation dans l’athérosclérose

A fundamental feature of atherosclerosis is a chronic inflammation of the arterial intima characterised by the accumulation of low-density lipoproteins and cells undergoing apoptosis. Such material can be subject to modifications if not efficiently cleared. For example, the LDL can become oxidised or the apoptotic cells necrotic, both of which are highly immunogenic and inflammatory. These modified, endogenous structures can generate an auto-immune or “sterile inflammation” response and are the targets of both innate and adaptive immunity. Therefore, one can refer to atherosclerosis, in part, as an auto-immune diseas

Impact de l apoptose du macrophage sur la progression de la plaque d athérome

Le processus d athérosclérose est marqué par un ensemble de réponses cellulaires et moléculaires qui conduisent à l instauration de réponses immuno-inflammatoires chroniques. Dans ce cadre, des questions ont émergé concernant l impact de la mort cellulaire du macrophage de la plaque d athérome sur le remodelage de la lésion mais aussi sur son possible rôle de régulateur des réponses inflammatoires et immunitaires. Toutefois, il existe peu de données ciblées reliant l apoptose du macrophage au développement de l athérosclérose. Dans ce cadre, les travaux de recherche abordés et développés dans cette thèse se sont orientés vers (i) l étude de l impact d une maladie auto-immune (lupus) due à un défaut d élimination des cellules apoptotiques sur le développement de l athérosclérose et (ii) le développement et l utilisation de modèles murins permettant d évaluer l impact de l apoptose du macrophage sur le développement des lésions d athérosclérose.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF