Fatty acids have biological activities that go far beyond their function as energy sources. A correct the dietary ratio between the nutritionally essential ω‐6 and ω‐3 polyunsaturated fatty acids (PUFA) is fundamental for the physiological production of second messengers, such as eicosanoids and other autacoids, and to ensure a controlled biological response to numerous physiological and pathological processes. Besides, PUFA, because of the unsaturation of their carbon chains, play an important role in maintaining the structure and a correct fluidity state of the membranes, the latter is a factor that directly regulates the activity of membrane-bound proteins, including ATPase pumps. However, the higher the degree of PUFA unsaturation the higher is their peroxidability. Lipid peroxidation (LPO) is a degrading process that, proceeding through a chain reaction mechanism, produces various cytotoxic and pro-inflammatory substances involved in the etiopathogenesis of numerous pathologies, including cerebro- and cardiovascular diseases and type 2 diabetes mellitus. Several studies suggest protective effects of PUFA on cardiometabolic risk, but in recent years some studies have also reported potential negative effects. Based on these premises I collaborated on four studies aimed at evaluating: i) the effects of dietary supplementation with a multivitamin and ω-3 PUFA (MVP) on maternal biomarkers during the second and third trimester of pregnancy; (ii) the effects of ω-3 PUFA enrichment in endothelial cell membranes on LPO and the activity of the Na, K pump, which plays an important role in regulating the vascular tone of endothelial myocytes; (iii) the effects of diet-induced weight loss on the lipid composition of lipoproteins, peripheral cytokine levels and metabolic endotoxemia in obese subjects with metabolic syndrome (MetS); and vi) the chemical characterization of plasma lipoproteins by Raman microspectroscopy (RS). The first was a multicenter, randomized, and parallel study demonstrating that MVP supplementation led to a significant increase in concentrations of erythrocytic docosahexaenoic acid (DHA), omega-3 index, and vitamin D levels, while it did not affect the state of oxidative stress during pregnancy. These findings are important considering the essential roles of DHA in the developing brain, in visual development, and immunomodulation of the fetus. The results of the second study showed that as concentrations of EPA and DHA increase, the degree of fluidity and susceptibility to peroxidation increases in endothelial cell membranes. Besides, it has been observed that Na, K pump activity peaked at a concentration of 3.75 μM of the two PUFA, and then gradually decreased. This study highlights that low concentration EPA and DHA minimizes peroxidation potential and optimizes pump activity. The third study revealed a caloric-restriction-induced substantial transfer of triacylglycerols from VLDL and LDL to HDL that could impair the functionality of the latter, along with positive effects on inflammatory markers in a small group of subjects with MetS. In addition, an interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of cholesteryl ester transfer protein, an enzyme with a key role in lipoprotein remodelling. Finally, the latest study allowed the determination of the chemical composition of the main classes of lipoproteins through RS identification and characterization of the spectra of cholesterol, triacylglycerols, apolipoproteins and carotenoids in a very small amount of samples. This study paves the way for the application of this technique in clinical nutritional studies and on a better understanding of several metabolic and pathological conditions.

FATTY ACIDS UNSATURATION AND OXIDATIVE STRESS IN MEMBRANE FUNCTION, PREGNANCY, AND METABOLIC SYNDROME / M. Della Porta ; tutors: R. Cazzola, L. Pinotti ; phd coordinator: L. Pinotti. - : . Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, 2021 Apr 12. ((33. ciclo, Anno Accademico 2020.

FATTY ACIDS UNSATURATION AND OXIDATIVE STRESS IN MEMBRANE FUNCTION, PREGNANCY, AND METABOLIC SYNDROME.

M. DELLA PORTA
2021-04-12

Abstract

Fatty acids have biological activities that go far beyond their function as energy sources. A correct the dietary ratio between the nutritionally essential ω‐6 and ω‐3 polyunsaturated fatty acids (PUFA) is fundamental for the physiological production of second messengers, such as eicosanoids and other autacoids, and to ensure a controlled biological response to numerous physiological and pathological processes. Besides, PUFA, because of the unsaturation of their carbon chains, play an important role in maintaining the structure and a correct fluidity state of the membranes, the latter is a factor that directly regulates the activity of membrane-bound proteins, including ATPase pumps. However, the higher the degree of PUFA unsaturation the higher is their peroxidability. Lipid peroxidation (LPO) is a degrading process that, proceeding through a chain reaction mechanism, produces various cytotoxic and pro-inflammatory substances involved in the etiopathogenesis of numerous pathologies, including cerebro- and cardiovascular diseases and type 2 diabetes mellitus. Several studies suggest protective effects of PUFA on cardiometabolic risk, but in recent years some studies have also reported potential negative effects. Based on these premises I collaborated on four studies aimed at evaluating: i) the effects of dietary supplementation with a multivitamin and ω-3 PUFA (MVP) on maternal biomarkers during the second and third trimester of pregnancy; (ii) the effects of ω-3 PUFA enrichment in endothelial cell membranes on LPO and the activity of the Na, K pump, which plays an important role in regulating the vascular tone of endothelial myocytes; (iii) the effects of diet-induced weight loss on the lipid composition of lipoproteins, peripheral cytokine levels and metabolic endotoxemia in obese subjects with metabolic syndrome (MetS); and vi) the chemical characterization of plasma lipoproteins by Raman microspectroscopy (RS). The first was a multicenter, randomized, and parallel study demonstrating that MVP supplementation led to a significant increase in concentrations of erythrocytic docosahexaenoic acid (DHA), omega-3 index, and vitamin D levels, while it did not affect the state of oxidative stress during pregnancy. These findings are important considering the essential roles of DHA in the developing brain, in visual development, and immunomodulation of the fetus. The results of the second study showed that as concentrations of EPA and DHA increase, the degree of fluidity and susceptibility to peroxidation increases in endothelial cell membranes. Besides, it has been observed that Na, K pump activity peaked at a concentration of 3.75 μM of the two PUFA, and then gradually decreased. This study highlights that low concentration EPA and DHA minimizes peroxidation potential and optimizes pump activity. The third study revealed a caloric-restriction-induced substantial transfer of triacylglycerols from VLDL and LDL to HDL that could impair the functionality of the latter, along with positive effects on inflammatory markers in a small group of subjects with MetS. In addition, an interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of cholesteryl ester transfer protein, an enzyme with a key role in lipoprotein remodelling. Finally, the latest study allowed the determination of the chemical composition of the main classes of lipoproteins through RS identification and characterization of the spectra of cholesterol, triacylglycerols, apolipoproteins and carotenoids in a very small amount of samples. This study paves the way for the application of this technique in clinical nutritional studies and on a better understanding of several metabolic and pathological conditions.
CAZZOLA, ROBERTA
PINOTTI, LUCIANO
PUFA; pregnancy; MetS; inflammation; lipoproteins; endothelial membranes; RS; Caloric restriction
Settore BIO/10 - Biochimica
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
FATTY ACIDS UNSATURATION AND OXIDATIVE STRESS IN MEMBRANE FUNCTION, PREGNANCY, AND METABOLIC SYNDROME / M. Della Porta ; tutors: R. Cazzola, L. Pinotti ; phd coordinator: L. Pinotti. - : . Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, 2021 Apr 12. ((33. ciclo, Anno Accademico 2020.
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/824544
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