ABSTRACT
Osteoarthritis (OA) is a complex joint disease that currently has no cure. OA involves metabolic disorders in chondrocytes and an imbalance between autophagy and apoptosis. As a common risk factor for OA, obesity induces changes in the fatty acid composition of synovial fluid, thereby disturbing chondrocyte homeostasis. However, whether unsaturated fatty acids affect the development of OA by regulating chondrocyte autophagy remains unclear. This study aimed to determine the effects of oleic and linoleic acids on chondrocyte autophagy and related mechanisms. Based on the mass spectrometry results, the levels of multiple unsaturated fatty acids, including oleic and linoleic acids, in the synovial fluid of patients with OA and obesity were significantly higher than those in patients with OA only. Moreover, we found that FOXO1 and SIRT1 were downregulated after oleic and linoleic acids treatment of chondrocytes, which inhibited chondrocyte autophagy. Importantly, the upregulation of SIRT1 and FOXO1 expression not only increased the level of autophagy but also improved the expression of chondrocyte extracellular matrix proteins. Furthermore, upregulated SIRT1 and FOXO1 expression alleviated the destruction of the articular cartilage in an OA rat model. Our results suggest that SIRT1/FOXO1 signaling can alleviate oleic acid- and linoleic acid-induced cartilage degradation both in vitro and in vivo and that the SIRT1/FOXO1 pathway may serve as an effective treatment target for inhibiting OA progression.
Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Rats , Animals , Chondrocytes/metabolism , Down-Regulation , Linoleic Acids/metabolism , Linoleic Acids/pharmacology , Sirtuin 1/genetics , Sirtuin 1/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Cartilage, Articular/metabolism , Apoptosis , Autophagy , Obesity/metabolism , Forkhead Box Protein O1/metabolismABSTRACT
BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for â¼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.
Subject(s)
Cardiolipins , Linoleic Acid , Male , Mice , Animals , Cardiolipins/metabolism , Mitochondria , Dietary Fats/metabolism , Fatty Acids/metabolism , Liver/metabolism , Diet , Phospholipids/metabolism , Linoleic Acids/metabolism , RespirationABSTRACT
Cholesterol is an essential component of cell membranes and serves as an important precursor of steroidal hormones and bile acids, but elevated levels of cholesterol and its oxidation products have been accepted as a risk factor for maintenance of health. The free and ester forms of cholesterol and fatty acids are the two major biological lipids. The aim of this hypothesis paper is to address the long-standing dogma that cholesterol is less susceptible to free radical peroxidation than polyunsaturated fatty acids (PUFAs). It has been observed that cholesterol is peroxidized much slower than PUFAs in plasma but that, contrary to expectations from chemical reactivity toward peroxyl radicals, cholesterol appears to be more readily autoxidized than linoleates in cell membranes. The levels of oxidation products of cholesterol and linoleates observed in humans support this notion. It is speculated that this discrepancy is ascribed to the fact that cholesterol and phospholipids bearing PUFAs are localized apart in raft and non-raft domains of cell membranes respectively and that the antioxidant vitamin E distributed predominantly in the non-raft domains cannot suppress the oxidation of cholesterol lying in raft domains which are relatively deficient in antioxidant.
Subject(s)
Linoleic Acid , Phospholipids , Humans , Phospholipids/metabolism , Linoleic Acid/metabolism , Lipid Peroxidation , Antioxidants/metabolism , Cholesterol/metabolism , Cell Membrane/metabolism , Fatty Acids, Unsaturated/metabolism , Linoleic Acids/metabolismABSTRACT
La importancia de la grasa en la dieta, y su papel en la prevención cardiovascular es uno de los tópicos nutricionales mejor estudiados y, a pesar de ello, está en continua revisión. Ahora ya conocemos, en especial gracias a los estudios relacionados con la dieta mediterránea, que es más importante la calidad de la grasa que la cantidad de su ingesta. En ese sentido, la grasa saturada y la grasa trans están implicadas en el riesgo aterogénico, por lo que se recomienda que para el diseño de una dieta sana dichos nutrientes se deben sustituir por hidratos de carbono complejos o por grasas insaturadas, manteniendo el consumo de grasa saturada en < 10% y el de trans en < 1% de la ingesta caló- rica. Estudios poblacionales recientes, en especial el estudio de Kuopio y los trabajos realizados con el modelo de dieta mediterránea, están afianzando cada vez más la importancia de las grasas monoinsaturadas y poliinsaturadas como nutrientes claves para la prevención de las enfermedades crónicas de las sociedades modernas. Por otra parte, un tipo especial de ácidos grasos poliinsaturados, los de la serie omega 3 (n-3), están gradualmente convirtiéndose en nutrientes claves de una dieta sana, especialmente en niños. Por ello parece razonable que 4 sociedades, fuertemente implicadas en difundir los beneficios de la dieta como herramienta para prevenir las enfermedades cardiovasculares, desarrollen un consenso para difundir los nuevos conocimientos sobre la importancia de conseguir un aporte equilibrado y adecuado de grasa en la dieta de las poblaciones industrializadas. Esto justifica este documento realizado por un grupo de expertos de la Sociedad Española de Arteriosclerosis, la Sociedad Española de Medicina Familiar y Comunitaria, la Aso - ciación Española de Pediatría, la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediá trica y la Sociedad Española de Dietética y Ciencias de la Alimentación, en un esfuerzo porque resulte un trabajo multidisciplinar, orientado tanto a los adultos como a los niños en distintos tramos de edad (AU)
Although dietary fat and its role in cardiovascular prevention has been one of the most extensively studied nutritional topics, it continues to be an ever-expanding research area. Particularly thanks to studies on Mediterranean diet, we now know that fat quality is more relevant than the amount of fat we eat in the diet. Thus, saturated and trans fats have been found to increase the risk of atherogenic disease. This is why it is recommended to substitute complex carbohydrates or unsaturated fat for unsaturated and trans fats with the aim of reducing saturated and trans fat intake to < 10% and < 1%, respectively, of the total calorie intake. Recent population studies, particularly that conducted in Kuopio, Finland, and those on Mediterranean diet, stress the important role of monounsaturated and polyunsaturated fats as key nutrients in preventing cardiovascular disease in modern societies. Furthermore, a special type of polyunsaturated fatty acids, i.e. those of the omega-3 (n-3) series, is increasingly becoming essential nutrients for a healthy diet, especially in the case of children. Therefore, there is a rationale for four the Scientific Societies that are strongly committed to disseminate the benefits of a healthy diet in preventing cardiovascular disease, and to prepare a joint statement with the purpose of spreading improved knowledge on the importance of changing to a healthy diet with a well-balanced fat intake for industrialized populations. Accordingly, a multidisciplinary panel of experts from the following institutions has developed the present joint statement targeted at both adults and children of different ages: Spanish Society of Arteriosclerosis, Spanish Society of Family and Community Medicine, Spanish Association of Paediatrics, Spanish Society of Gastroenterology, Hepatology and Paediatric Nutrition and Dietetics, and Spanish Society for Food Sciences (AU)
Subject(s)
Humans , Male , Female , Child , Adult , Dietary Fats/adverse effects , Cardiovascular Diseases/prevention & control , Risk Factors , Fatty Acids, Monounsaturated/metabolism , Linoleic Acids/metabolism , Overweight/prevention & control , Feeding BehaviorABSTRACT
La importancia de la grasa en la dieta, y su papel en la prevención cardiovascular es uno de los tópicos nutricionales mejor estudiados y, a pesar de ello, está en continua revisión. Ahora ya conocemos, en especial gracias a los estudios relacionados con la dieta mediterránea, que es más importante la calidad de la grasa que la cantidad de su ingesta. En ese sentido, la grasa saturada y la grasa trans están implicadas en el riesgo aterogénico, por lo que se recomienda que para el diseño de una dieta sana dichos nutrientes se deben sustituir por hidratos de carbono complejos o por grasas insaturadas, manteniendo el consumo de grasa saturada en < 10% y el de trans en < 1% de la ingesta calórica. Estudios poblacionales recientes, en especial el estudio de Kuopio y los trabajos realizados con el modelo de dieta mediterránea, están afianzando cada vez más la importancia de las grasas monoinsaturadas y poliinsaturadas como nutrientes claves para la prevención de las enfermedades crónicas de las sociedades modernas. Por otra parte, un tipo especial de ácidos grasos poliinsaturados, los de la serie omega 3 (n-3), están gradualmente convirtiéndose en nutrientes claves de una dieta sana, especialmente en niños. Por ello parece razonable que 4 sociedades, fuertemente (..) (AU)
Although dietary fat and its role in cardiovascular prevention has been one of the most extensively studied nutritional topics, it continues to be an everexpading research area. Particularly thanks to studies on Mediterranean diet, we now know that fat quality is more relevant than the amount of fat we eat in the diet. Thus, saturated and trans fats have been found to increase the risk of atherogenic disease. This is why it is recommended (..) (AU)
Subject(s)
Humans , Dietary Fats/pharmacokinetics , Diet, High-Fat/adverse effects , Cardiovascular Diseases/physiopathology , Fatty Acids/metabolism , Fatty Acids, Monounsaturated/metabolism , Linoleic Acids/metabolism , MargarineABSTRACT
Se estudió el efecto de la administración de aceite de maíz con la dieta sobre el metabolismo de los ácidos grasos esenciales (AGE) en lactantes normales y desnutridos alimentados solamente con leche de vaca desde el nacimiento. Se seleccionó también un grupo de lactantes alimentados con leche materna. Se usó como parámetro bioquímico para evaluar las condiciones en que se encontraban los AGE la composición en ácidos grasos de los fosfolípidos del plasma. Se observó un cuadro consistente con una carencia en AGE tanto en lactantes normales como desnutridos alimentados con leche de vaca, es decir, una disminución de la proporción de los ácidos grasos de la serie n6 y un aumento de los ácidos grasos saturados. Calculando la relación precursor-productos de los ácidos polietilénicos se observó una alteración del metabolismo del ácido linoleico. La administración del aceite de maíz restauró el perfil de los ácidos grasos a valores normales aun en los lactantes desnutridos a pesar de que el síndrome clínico de la desnutrición no había sido corregido (AU)
Subject(s)
Infant, Newborn , Infant , Comparative Study , Humans , Male , Female , Milk/chemistry , Phospholipids/metabolism , Fatty Acids, Essential/metabolism , Protein-Energy Malnutrition/metabolism , Corn Oil/metabolism , Corn Oil/analysis , Phospholipids/blood , Fatty Acids, Essential/blood , Linoleic Acids/metabolism , Food, Fortified , Chromatography, Gas , Milk, Human/chemistryABSTRACT
Se estudió el efecto de la administración de aceite de maíz con la dieta sobre el metabolismo de los ácidos grasos esenciales (AGE) en lactantes normales y desnutridos alimentados solamente con leche de vaca desde el nacimiento. Se seleccionó también un grupo de lactantes alimentados con leche materna. Se usó como parámetro bioquímico para evaluar las condiciones en que se encontraban los AGE la composición en ácidos grasos de los fosfolípidos del plasma. Se observó un cuadro consistente con una carencia en AGE tanto en lactantes normales como desnutridos alimentados con leche de vaca, es decir, una disminución de la proporción de los ácidos grasos de la serie n6 y un aumento de los ácidos grasos saturados. Calculando la relación precursor-productos de los ácidos polietilénicos se observó una alteración del metabolismo del ácido linoleico. La administración del aceite de maíz restauró el perfil de los ácidos grasos a valores normales aun en los lactantes desnutridos a pesar de que el síndrome clínico de la desnutrición no había sido corregido
Subject(s)
Infant, Newborn , Infant , Humans , Male , Female , Fatty Acids, Essential/metabolism , Protein-Energy Malnutrition/metabolism , Milk/chemistry , Corn Oil/metabolism , Phospholipids/metabolism , Fatty Acids, Essential/blood , Linoleic Acids/metabolism , Chromatography, Gas , Food, Fortified , Milk, Human/chemistry , Corn Oil/analysis , Phospholipids/bloodABSTRACT
Preliminary studies suggest that in the indigenous Bahamian population hypertensive cardiovascular disease is a prominent cause of morbidity and mortality; however, coronary heart disease is rarely diagnosed. On the basis of the high linoleic acid content in the adipose tissue of the Bahamian children and adults compared to Americans, the hypothesis is proposed that in Bahamians, dietary sources of linolic acid modify the effect of hypertension as a risk factor predisposing to coronary heart disease (AU)