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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty acid overload has been proposed as a cause of decreased responsiveness in the major insulin target tissues of the body such as muscle and liver tissue. We therefore investigated fatty acid oxidation in soleus muscle and liver isolated from Zucker diabetic fatty (ZDF) rats treated with thiazolidinediones, a new class of antidiabetic agents. 14CO2 production from [14C]palmitic (C16:0) acid was lower in the soleus muscle and liver of ZDF rats versus lean rats (P < .05). When administered orally to ZDF rats for 2 weeks, the thiazolidinediones troglitazone (300 mg/kg) and KRP-297 (10 mg/kg) increased palmitic acid oxidation in the soleus muscle of ZDF rats (P < .05). KRP-297, but not troglitazone, increased palmitic acid oxidation in the liver of ZDF rats (P < .05), and both troglitazone and KRP-297 inhibited triglyceride accumulation in the skeletal muscle of ZDF rats. Hepatic triglyceride accumulation in ZDF rats was inhibited by KRP-297, but not by troglitazone. A reduction of fatty acid oxidation in the liver of ZDF rats and an increase in response to KRP-297 were observed only when C16:0 and C18:0 fatty acids, not C8:0, were used as substrates. Thus, there were defects in fatty acid catabolic activity and triglyceride accumulation in the soleus muscle and liver of ZDF rats. These results indicate that KRP-297 has advantages over troglitazone in the amelioration of these lipid metabolic abnormalities in insulin resistance associated with obesity.
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PMID:Tissue-specific actions of antidiabetic thiazolidinediones on the reduced fatty acid oxidation in skeletal muscle and liver of Zucker diabetic fatty rats. 1077 79

Obesity is associated with insulin resistance and some reproductive abnormalities. Circulating FFAs are often elevated in obese subjects and are also closely linked to insulin resistance. In this study, we demonstrated that saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated FFA, arachidonic acid, had no effect on the cell survival, even at supraphysiological concentrations. The suppressive effect of saturated FFAs on cell survival was caused by apoptosis, as evidenced by DNA ladder formation and annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of palmitic acid and stearic acid were unrelated to the increase of ceramide generation or nitric oxide production and were also completely blocked by Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was consistent with the effect of the respective FFA form. Surprisingly, arachidonic acid instead showed a protective effect on palmitic acid- and stearic acid-induced cell apoptosis. A Western blot analysis showed the apoptosis of the granulosa cells induced by palmitic acid to be accompanied by the down-regulation of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector, Bax. These results indicate that saturated FFAs induce apoptosis in human granulosa cells caused by the metabolism of the respective acylcoenzyme A form, and the actual composition of circulating FFAs may thus play a critical role in the apoptotic events of human granulosa cells. These effects of FFAs on granulosa cell survival may be a possible mechanism for reproductive abnormalities, such as amenorrhea, which is frequently observed in obese women.
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PMID:Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. 1145 7

Phytanic acid is a derivative of the phytol side-chain of chlorophyll. It appears in humans following the ingestion of fat-containing foods and is present in human blood at a low micromolar concentration. It may activate retinoid X receptors (RXR) or peroxisome proliferator-activated receptor (PPAR) alpha in vitro. Phytanic acid induced the adipocyte differentiation of 3T3-L1 cells in culture as assessed by accumulation of lipid droplets and induction of the aP2 mRNA marker. This effect was mimicked by a synthetic activator of RXR but not by a PPARalpha agonist or by palmitic acid. In human pre-adipocytes in primary culture, phytanic acid also induced adipocyte differentiation. These findings indicate that phytanic acid may act as a natural rexinoid in adipose cells and suggest a potential use in the treatment of human type 2 diabetes and obesity.
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PMID:The chlorophyll-derived metabolite phytanic acid induces white adipocyte differentiation. 1218 8

In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.
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PMID:Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. 1268 33

We investigated whether fuel metabolism prior to high-fat feeding differs in outbred Sprague-Dawley rats either prone or resistant to diet-induced obesity. Chow-fed rats were deprived of food, and blood was collected 12, 18, and 24 h later. Rats were then fed a high-fat diet ad libitum for up to 4 weeks to assess weight gain. Blood samples were analyzed for a variety of metabolic fuels and hormones. Only fasting plasma triglyceride concentrations showed a positive correlation with the weight gain during the high-fat feeding period, with concentrations after 18 h of fasting showing the most consistent relationship to weight gain. Body weights and fat pad weights did not correlate with fasting plasma triglyceride concentrations before high-fat feeding. The amount of 14CO(2) recovered from gavaged [14C]palmitic acid in chow-fed rats negatively correlated with weight gain during the subsequent period of high-fat feeding. These results show that there are preexisting differences in fat catabolism that may underlie differential susceptibility to diet-induced obesity; in particular, fasting levels of plasma triglycerides and fatty acid oxidation may be early predictive markers for this susceptibility.
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PMID:Fasting plasma triglyceride levels and fat oxidation predict dietary obesity in rats. 1278 34

Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic beta-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of beta-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in beta-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to beta-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased beta-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease beta-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet beta-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the beta-cell.
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PMID:Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity. 1456 Dec 12

In preliminary experiments, polyphenol fractions prepared from the leaves of Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at 3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a dose of 570 mg/kg. The present study examined the anti-obesity action of polyphenol fractions of S. matsudana leaves by testing whether the polyphenol fractions prevented the obesity induced by feeding a high-fat diet to female mice for 9 weeks. Body weights at 2-9 weeks and the fi nal parametrial adipose tissue weights were significantly lower in mice fed the high-fat diet with 5% polyphenols of S. matsudana leaves than in those fed the high-fat diet alone. The polyphenols of S. matsudana leaves also significantly reduced the hepatic total cholesterol content, which was elevated in mice fed the high-fat diet alone. In addition, the polyphenol fractions of S. matsudana leaves inhibited palmitic acid uptake into brush border membrane vesicles prepared from rat jejunum and alpha-amylase activity, and their fractions enhanced norepinephrine-induced lipolysis in fat cells. In conclusion, it is suggested that the inhibitory effects of the flavonoid glycoside fraction of S. matsudana leaves on high-fat diet-induced obesity might be due to the inhibition of carbohydrate and lipid absorption from small intestine through the inhibition of alpha-amylase and palmitic acid uptake into small intestinal brush border membrane or by accelerating fat mobilization through enhancing norepinephrine-induced lipolysis in fat cells.
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PMID:Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by polyphenols of Salix matsudana in high fat-diet treated rodent animals. 1466 54

Fat oxidation is important for maintaining health and for supplying energy for exercise. We have proposed that the predisposition for individual rates of fat oxidation is determined genetically but may be modulated by acute exercise or exercise training. The purpose of this study was to examine cellular fat oxidation in white blood cells (WBC) using [9,10-3H]palmitic acid. Sedentary controls free of symptoms (SED-C, n=32), were compared with known carnitine palmitoyltransferase (CPT) II-deficient patients (n =2), patients with fatiguing diseases (chronic fatigue syndrome, CFS, n=6; multiple sclerosis, MS, n=31), obesity (OB, n=5), eating disorders (ED, n=16), sedentary individuals prior to and after exercise (SED-Ex, n=12), exercise-trained sedentary individuals (SED-Tr, n=12), and elite runners (ER, n=5). Fat oxidation in WBC for all subjects was normally distributed (mean=0.270 +/- 0.090 nmol/h per 10(9) WBC) and ranged from 0.09 nmol/h per 10(9) WBC in CPT II-deficient patients to 0.59 nmol/h per 10(9) WBC in ER. There were no significant sex or acute exercise effects on WBC fat oxidation. Patients with MS, OB or ED were not different from SED-C; however, in CPT II-deficient patients, fat oxidation was low, while that of CFS patients was high. Exercise training in SED-C resulted in a 16% increase in fat oxidation but in ER it was still 97% higher than in SED-C. We propose that while WBC fat oxidation is not significantly affected by sex or acute exercise, and only by 15-20% with training, genetic factors play a role in determining both high and low fat oxidation in certain groups of individuals. The genetic predisposition for individual rates of fat oxidation may be easily measured using WBC fat oxidation, as has been shown for CPT II-deficient patients and for elite runners. Ranges of WBC fat oxidation that are abnormally low (<20 nmol/h per 10(9) WBC, normal 20-35) or high (>35 nmol/h per 10(9) WBC) are proposed based on genetic factors evaluated in this study.
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PMID:The distribution of white blood cell fat oxidation in health and disease. 1497 Jul 49

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.
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PMID:Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome. 1501 42

We recently described a primarily reduced palmitate oxidation in myotubes established from type 2 diabetic subjects, whereas triacylglycerol (TAG) accumulation seemed to be adaptive. However, it is still uncertain whether these changes are similar for saturated and unsaturated fatty acids and whether high concentrations of glucose and/or insulin may change this picture. Studies of palmitic acid and oleic acid metabolism in human myotubes established from control and type 2 diabetic subjects under conditions of acute high concentrations of insulin and/or glucose may solve these questions. Total oleic acid and palmitic acid uptake in myotubes was increased during acute insulin stimulation (P < 0.01) but not under acute, high-glucose concentrations, and no differences were found between the groups. Type 2 diabetic myotubes expressed a reduced palmitic acid oxidation to carbon dioxide (P </= 0.04), whereas oleic acid oxidation showed no differences between myotubes from both groups. High glucose concentrations decreased oleic acid oxidation (P </= 0.03). Lipid distribution was not different in diabetic and control myotubes when palmitic acid and oleic acid incorporation into cellular lipids was compared. Myotubes that were exposed to palmitic acid showed an increased palmitic acid incorporation into diacylglycerol (DAG) and TAG compared with myotubes that were exposed to oleic acid (P < 0.05) expressing an increased intracellular free fatty acid (FFA) level (P < 0.05). Lipid distribution was not affected by high glucose, whereas insulin increased FFAs, DAG, and TAG (P < 0.05). De novo lipid synthesis from glucose in both diabetic and control myotubes was of the same magnitude independent of glucose and insulin concentrations. These results indicate that palmitic acid and oleic acid are utilized in the same pattern in diabetic and control myotubes even though palmitic acid oxidation is primarily reduced in diabetic cells. Palmitic acid and oleic acid are handled differently by myotubes: Palmitic acid seems to accumulate as DAG and TAG, whereas oleic acid accumulates as intracellular FFAs. These observations indicate that oleic acid is preferable as fatty acid as it accumulates to a lesser extent as DAG and TAG than palmitic acid. Neither acute hyperglycemia nor de novo lipid synthesis from glucose seems central to the TAG accumulation in obesity or type 2 diabetes.
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PMID:Differential utilization of saturated palmitate and unsaturated oleate: evidence from cultured myotubes. 1573 39


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