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Currently there are no established guidelines regarding the use of long-chain triglycerides (LCT) vs. medium-chain triglycerides medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) in total parenteral nutrition (TPN). Severe malnutrition of patients with refractory cachexia (RC) often causes their disqualification from invasive methods of treatment thus decreasing their quality of life and survival time.
A comprehensive survey on triglycerides (TAGs) of bovine milk was conducted by a combination of exhaustive liquid chromatography (LC) separation, high-resolution mass spectrometry (MS) detection, and automated lipid molecular feature extraction. A total of 220 groups (a series of species having the same chemical formula and mass) and 3454 molecular species of TAGs were identified based on the accurate mass of the parent ion as well as MS2 information. Sixty-five different fatty acids (FAs) were found across these TAG species; C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, and C18:1 were the most frequent FAs, whereas C11:3, C11:4, C27:0, C27:1, C28:0, and C28:1 were rare FAs in TAG molecules. The number of species identified represents only a small portion of total TAG molecules that can be theoretically synthesized from 65 FAs. Each TAG group contains on average 15-16 isomeric species (species with different FA composition), but positional isomers do not seem to be widespread. As the isomeric species cannot be completely resolved chromatographically, quantification of TAG was conducted at the group level. The most abundant TAG groups in bovine milk include TAG 34:0, TAG 36:0, TAG 38:1, TAG 38:0, and TAG 40:1. This study provides the most comprehensive milk TAG inventory so far that can be used as a reference for studying milk lipids.
Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.
Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.
Although intraocular pressure is the main the risk factor for the development of glaucoma, other risk factors such as vascular dysfunction might play an additional pathogenic role. Hypertriglyceridemia, which may lead to vascular dysfunction, has been implicated in the development of glaucoma. The objective of this meta-analysis was to investigate the association of triglyceride levels with the risk of glaucoma in case-control studies. Seventeen case-control studies were included investigating the difference in triglyceride levels in patients with glaucoma (N = 1 391) compared to subjects without glaucoma (N = 25 575). In random effects meta-analysis, the pooled mean triglyceride level across all studies and patients with and without glaucoma was 132.9 mg/dL (95%CI: 124.0-141.7). Patients with glaucoma had significantly higher mean triglyceride levels than patients without glaucoma (absolute difference = 14.2 mg/dL, 95%CI: 5.8-22.5, p < 0.0001). A considerable amount of heterogeneity of included studies was observed (I2 = 66.2%, heterogeneity χ2 = 47.4 on 16 degrees of freedom, p < 0.0001). In conclusion, this meta-analysis of case-control studies found that patients with glaucoma had higher mean triglyceride levels than patients without glaucoma. This finding is consistent with the concept that hypertriglyceridemia represents an additional risk factor for glaucoma. Whether this association is causal and/or might be modified by glaucoma medications remains to be investigated.
Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown.
While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL-triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by 1H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by 1H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction.
The prevalence of obesity-related disorders has been steadily increasing over the past couple of decades. Diseases that were once only detected in adults are now prevalent in children, such as hyperlipidemia. The adipose tissue-derived hormonal factor C1q TNF Related Protein 3 (CTRP3) has been linked to triglyceride regulation especially in animal models. However, the relationship between circulating CTRP3 levels and obesity-related disorders in human subjects is controversial. CTRP3 can circulate in different oligomeric complexes: trimeric (<100 kDa), middle molecular weight (100-300 kDa), and high molecular weight (HMW) oligomeric complexes (>300 kDa). Previous work has identified that it is not the total amount of CTRP3 present in the serum, but the specific circulating oligomeric complexes that appear to be indicative of the relationship between CTRP3 and serum lipids levels. However, this work has not been examined in children. Therefore, the purpose of this study was to compare the levels of different oligomeric complexes of CTRP3 and circulating lipid levels among young children (aged 7-10 years).
Cardiovascular damages poses risks to children with Kawasaki disease (KD). Although hypertriglyceridemia and hypercholesteremia are risk factors of cardiovascular damages, studies on the blood lipid metabolism in KD are still limited. This study aims to analyze the blood lipids and coagulation in KD.
Ketones provide an alternative brain fuel and may be neuroprotective in older people. Little is known of how to optimize the ketogenic effect of C8:0-C10:0 medium chain triglyceride supplement (kMCT). Metabolic switching (MS) from glucose to ketones as a fuel may have metabolic benefits but has not been extensively studied in humans. The objective of the present study was to use an 8 h metabolic study day protocol to assess the influence of typical components of MS, including a kMCT supplement, low-carbohydrate meal and meal timing, on blood ketones, glucose, insulin and free fatty acids (FFA). In one test, the effect of age was also investigated. Over the 8 h metabolic study day, two 10 g doses of the kMCT increased the plasma ketone response by 19% while reducing overall glycemia by 12% without altering insulin or FFA levels. Moreover, a single early meal (breakfast but no lunch) potentiated the ketogenic effect of MS over 8 h, compared to a single delayed meal (lunch but no breakfast). Age and the low carbohydrate meal did not affect the ketones response. We conclude that an 8-h test period can be used to assess metabolic changes during short-term MS. kMCT provide a robust short-term increase in ketones and might enhance the metabolic effectiveness of short-term or intermittent fasting as a component of MS.
The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR-HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3-PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.HDAC3 is a critical mediator of hepatic lipid metabolism and its loss leads to fatty liver. Here, the authors characterize the liver HDAC3 interactome in vivo, provide evidence that HDAC3 interacts with PROX1, and show that HDAC3 and PROX1 control expression of genes regulating lipid homeostasis.
Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis.
Exercise is a well-established tool for cardiovascular risk reduction. Particularly eccentric exercise, which essentially means walking downwards could favour more people becoming physically active. With the present controlled study, we tested the hypothesis that eccentric exercise can improve insulin sensitivity, triglyceride handling, body mass index, glucose tolerance and inflammation. We allocated 127 healthy sedentary individuals to one of two groups: (i) an active group of 102 individuals walking downwards a predefined route three to five times per week over two months, covering a difference in altitude of 540 m; for the upward route a cable car was used, for which adherence was recorded electronically and (ii) a matched control group of 25 individuals who stayed sedentary. Fasting and postprandial metabolic profiles were obtained at baseline and after two months. Compared to baseline, eccentric exercise significantly improved HOMA insulin resistance (1.94 ± 1.65 vs. 1.71 ± 1.36 (µU-1 ml) × ((mmol/l)-122.5); p = 0.038) and resulted in a decrease in fasting glucose (97 ± 15 vs. 94 ± 9 mg dl-1; p = 0.025) and glucose tolerance (238 ± 50 vs. 217 ± 47 mg dl-1 h-1; p < 0.001), whereas these parameters did not change significantly in the control group. Eccentric exercise significantly improved triglyceride tolerance (1923 ± 1295 vs. 1670 ± 1085 mg dl-1 h-1; p = 0.003), whereas triglyceride tolerance remained unchanged in the control group (p = 0.819). Furthermore, body mass index (27.7 ± 4.3 vs. 27.4 ± 4.3 kg m-2; p = 0.003) and C-reactive protein (0.27 ± 0.42 vs. 0.23 ± 0.25 mg dl-1; p = 0.031) were significantly lowered in the eccentric exercise group but not in the control group. Downhill walking, a type of exercise is a promising unusual exercise modality with favorable effects on body mass index, insulin action, on postprandial glucose and triglyceride handling and on C-reactive protein.ClinicalTrials.gov Identifier: NCT00386854.
The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun.2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.
Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid metabolome in response to EMS consumption.
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