Plasma Free Fatty Acid Levels Research Articles

Exercise increases plasma THC concentrations in regular cannabis users

BackgroundThe major psychoactive ingredient of cannabis, Δ9-tetrahydrocannabinol (THC) accumulates in fat tissue from where it slowly diffuses back into blood. THC pre-treated rats can show elevated plasma cannabinoid levels when subjected to conditions that promote fat utilization, such as fasting. Here we examine whether fasting and exercise increase plasma THC concentrations in regular cannabis users. MethodsFourteen regular cannabis users completed 35min of exercise on a stationary bicycle in either a fed or overnight fasted state. Plasma cannabinoid levels were assessed prior to exercise, immediately post-exercise and 2h post-exercise. Plasma samples were also analyzed for indices of lipolysis (free fatty acids (FFA) and glycerol). ResultsExercise induced a small, statistically significant increase in plasma THC levels accompanied by increased plasma FFA and glycerol levels. Exercise-induced increases in plasma THC concentrations were positively correlated with body mass index. Fasting induced a significant increase in plasma FFA levels, and a lowering of blood glucose, but did not significantly alter plasma cannabinoid levels. ConclusionsHere we demonstrate that exercise enhances plasma THC levels in regular cannabis users. The lack of a fasting effect may reflect the modest duration of fasting used which was associated with only a modest increase in fat utilization relative to exercise. Overall, these results suggest that exercise may elevate blood THC levels by releasing dormant THC from fat stores. These data suggest the interpretation of blood THC levels in roadside and workplace tests might be complicated by recent exercise.

A beverage of Asiatic plantain extracts alleviated postprandial oxidative stress in overweight hyperlipidemic subjects challenged with a high-fat meal: a preliminary study

There is emerging interest in the potential of the phenolic compounds of Asiatic plantain (Plantago asiatica L.) to attenuate in vitro and in vivo oxidative stress. We hypothesized that a single administration of Asiatic plantain beverage may exert protective effects against postprandial oxidative stress. This preliminary study was designed to compare the ability of different doses of Asiatic plantain beverage to mitigate the postprandial effects of a high-fat meal on the oxidation of lipids and DNA in overweight hyperlipidemic subjects. In a randomized, double-blind, placebo-controlled parallel design (n = 10/group), 40 subjects were administered a single high-fat meal with either a placebo or 1 of 3 Asiatic plantain extract beverages (low, intermediate, or high dose). Blood samples were obtained at fasting and 60, 120, 240, and 360 minutes (total of 5 samples) after intervention. The data showed a tendency for plasma free fatty acid levels to decrease in response to high-dose Asiatic plantain at all time points. Plasma oxidized low-density lipoprotein levels were significantly reduced with high-dose Asiatic plantain at 120 minutes (P = .0251 vs placebo). A comet assay revealed that DNA damage in lymphocytes was significantly decreased by Asiatic plantain at 360 minutes (P = .0225 vs placebo). There were no treatment differences in triglyceride or malondialdehyde levels. The maximum suppression was achieved with a high dose (20 g Asiatic plantain extract/80 mL). These results suggest that by protecting low-density lipoprotein and DNA, an Asiatic plantain beverage may be useful to enhance antioxidant.

Why Does Obesity Increase the Risk for Cardiovascular Disease?

Insulin resistance and inflammation are recognized as important links between obesity and cardiovascular disease (CVD). Plasma free fatty acids (FFA), either released from the abnormally enlarged adipose tissue or as part of the excessive nutrient intake, produce insulin resistance and inflammation. Both insulin resistance and inflammation are tightly linked to several independent CVD risk factors such as type 2 diabetes (T2DM), hypertension, dyslipidemia and disorders of blood coagulation. Several hypotheses have been proposed to explain how increased plasma FFA levels can cause insulin resistance including a) the lipid metabolite hypothesis, b) the inflammation hypothesis, c) the hyperinsulinemia hypothesis and d) the endoplasmic reticulum (ER) stress hypothesis. The latter does not require presence of elevated plasma FFA levels and thus provides a mechanism to explain the development of insulin resistance and inflammation in all obese individuals, i.e., those with and without elevated plasma FFA levels. Hyperinsulinemia per se has been suspected to cause CVD based on epidemiologic studies which have associated chronic hyperinsulinemia with CVD without, however, establishing a cause and effect relationship. There are, however, newer results which support the hypothesis that chronic hyperinsulinemia per se can promote the development of CVD. For instance, hyperinsulinemia can activate triglyceride formation, several matrix metalloproteinases (MMP), and the tissue factor pathway of blood coagulation, all of which are known to be associated with CVD, even in the presence of "metabolic insulin resistance".

Adrenergic Activation, Fuel Substrate Availability, and Insulin Resistance in Patients With Congestive Heart Failure

This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF). Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated. Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography. Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p = 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p = 0.069). CRI correlated with the exercise-induced increase in FFA (r = 0.41; p < 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group. Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.

Effects of isotonic and isometric exercises with mist sauna bathing on cardiovascular, thermoregulatory, and metabolic functions

To clarify the effects of isometric and isotonic exercise during mist sauna bathing on the cardiovascular function, thermoregulatory function, and metabolism, six healthy young men (22 ± 1 years old, height 173 ± 4 cm, weight 65.0 ± 5.0 kg) were exposed to a mist sauna for 10 min at a temperature of 40 °C, and relative humidity of 100 % while performing or not performing ∼30 W of isometric or isotonic exercise. The effect of the exercise was assessed by measuring tympanic temperature, heart rate, systolic and diastolic blood pressure, chest sweat rate, chest skin blood flow, and plasma catecholamine and cortisol, glucose, lactate, and free fatty acid levels. Repeated measures ANOVA showed no significant differences in blood pressure, skin blood flow, sweat rate, and total amount of sweating. Tympanic temperature increased more during isotonic exercise, and heart rate increase was more marked during isotonic exercise. The changes in lactate indicated that fatigue was not very great during isometric exercise. The glucose level indicated greater energy expenditure during isometric exercise. The free fatty acid and catecholamine levels indicated that isometric exercise did not result in very great energy expenditure and stress, respectively. The results for isotonic exercise of a decrease in lactate level and an increase in plasma free fatty acid level indicated that fatigue and energy expenditure were rather large while the perceived stress was comparatively low. We concluded that isotonic exercise may be a more desirable form of exercise during mist sauna bathing given the changes in glucose and free fatty acid levels.

S 50131 and S 51434, two novel small molecule glucokinase activators, lack chronic efficacy despite potent acute antihyperglycaemic activity in diabetic mice

Small molecule glucokinase activators (GKAs) have been associated with potent antidiabetic efficacy and hepatic steatosis in rodents. This study reports the discovery of S 50131 and S 51434, two novel GKAs with an original scaffold and an atypical pharmacological profile. Activity of the compounds was assessed in vitro by measuring activation of recombinant glucokinase, stimulation of glycogen synthesis in rat hepatocytes and increased insulin secretion from rat pancreatic islets of Langerhans. Efficacy and safety in vivo were evaluated after oral administration in db/db mice by measuring glycaemia, HbA1c and dyslipidaemia-associated events. S 50131 and S 51434 activated GK and stimulated glycogen synthesis in hepatocytes and insulin secretion from pancreatic islets. Unexpectedly, while both compounds effectively lowered glycaemia after acute oral administration, they did not decrease HbA1c after a 4-week treatment in db/db mice. This lack of antidiabetic efficacy was associated with increased plasma free fatty acids (FFAs), contrasting with the effect of GKA50 and N00236460, two GKAs with sustained HbA1c lowering activity but neutral regarding plasma FFAs. S 50131, but not S 51434, also induced hepatic steatosis, as did GKA50 and N00236460. However, a shorter, 4-day treatment resulted in increased hepatic triglycerides without changing the plasma FFA levels, demonstrating dynamic alterations in the lipid profile over time. In addition to confirming the occurrence of dyslipidaemia with GKAs, these findings provide new insights into understanding how such compounds may sustain or lose efficacy over time.

High FFA levels related to microalbuminuria and uncoupling of VEGF-NO axis in obese rats

The objectives of this study were to test whether elevated free fatty acids (FFA) from visceral fat accumulation is related to increased urinary albumin excretion and whether fenofibrate has renal protective effects by regulating vascular endothelial growth factor-nitric oxide (VEGF-NO) axis in rats with diet-induced obesity. Wistar rats were randomly divided into groups fed a normal diet, a high-fat diet, and a high-fat diet plus fenofibrate. Blood and urine samples were collected. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV) of the aorta. Renal tissues were collected for CD31 immunohistochemistry. Glomerular NO and VEGF expression were measured by Griess reaction and Western blot, respectively. At the end of 24 weeks, plasma FFA and triglyceride levels significantly increased in the obese rats. Fenofibrate intervention decreased serum FFA and triglyceride levels by 43.4 and 48 %, respectively, accompanied by a reduced visceral fat index. Urinary albumin/creatinine ratio increased in obese rats, which decreased 62.6 % after fenofibrate intervention. Severe EDV impairment was observed in obese rats; this was partially improved by fenofibrate. CD31 expression in glomeruli increased in obese rats, indicating increased endothelial cell proliferation. Obese rats showed increased glomerular VEGF expression and reduced NO levels. This uncoupling of VEGF-NO axis was partially improved by fenofibrate. Elevated circulating FFA level may cause increased microalbuminuria in obese rats due to impairment of EDV; increased microalbuminuria can be improved by fenofibrate intervention. The mechanism may be related to FFA-induced uncoupling of VEGF-NO axis and endothelial dysfunction.

ASSA13-16-4 The Influence of Combination of Amlodipine and Valsartan on Plasma Free Fat Acid and Adiponectin in Patients with Essential Hypertension

<h3>Objective</h3> To investigate the influence of combination therapy of amlodipine and valsartanon on the plasma adiponectin (ADPN) and free fatty acids (FFAs) levels in patients with essential hypertension. <h3>Methods</h3> Fifty hypertensive patients were included. After 4 week amlodipine (5mg/d) treatment, 34 patients with diastolic blood pressure (DBP) equal to or more than 90 mmHg were included in the double blind period and randomly divided into amlodipine (amlodipine, 5mg/d) and the combination (amlodipine 5mg + valsartan 80 mg/d) groups for other 8 weeks. BP, blood lipids, blood glucose, ADPN and FFA were measured at baseline, 4 and 12 week after treatment. Eighteen normotensive adults were selected as the control. <h3>Results</h3> At baseline, FFA, total cholesterol (TC) and triglycerides (TG) were significantly higher, but ADPN lower in the hypertensive group than in the control group. Four weeks amlodipine treatment increased significantly ADPN levels (4.75 ± 1.88 vs 5.09 ± 1.97 mg/L, P. <h3>Conclusions</h3> Four weeks amlodipine monotherapy can significantly increase the plasma ADPN level. On this base, the combination therapy of amlodipine and valsartan can better improve plasma ADPN and FFA than amlodipine monotherapy.

Sex differences in exercise-induced cardiac hypertrophy

Physiological cardiac hypertrophy (PCH), induced by intensive exercise or pregnancy, differs substantially from the pathological form of myocardial hypertrophy, accruing after aortic stenosis or chronic arterial hypertension. In contrast to pathological forms of cardiac hypertrophy, exercise-induced increase of left ventricular mass is related to cardiac myocytes enlargement, with no apparent sign of fibrosis or apoptosis, and does usually not result in cardiac failure. Recently published results obtained from various animal studies documented clear sex-specific regulation of exercise-induced cardiac hypertrophy in rodents, with a pronounced hypertrophic response to training load observed in female animals when compared to male littermate. In addition to increased cardiac hypertrophic response, females exhibited augmented lipolytic activity measured in adipose tissue in response to exercise, resulting in increased plasma free fatty acid levels, measured after training. Importantly, sex-specific differences in adipose tissue lipolysis and systemic fat metabolism induced by intensive training were also confirmed in human studies, performed on athletes and healthy volunteers. Since development of PCH during the physical training is accompanied by enhanced fatty acid oxidation and reduced glucose uptake, intensive lipolytic activity, measured in female adipose tissue could explain, at least in part, sex-specific differences observed in hypertrophic response to exercising. Given that sex hormones, such as estrogens and testosterone, in addition to their role in the regulation of adipose tissue metabolism, were also reported to modulate development of pathological myocardial hypertrophy, one may expect also a putative contribution of sex hormones in processes regulating the development and progression of PCH.

The vascular endothelium in diabetes and its potential as a therapeutic target

The vascular endothelium in diabetes and its potential as a therapeutic target

Angiopoietin-like Protein 4 and the level of Free Fatty Acids in Human Blood Plasma: Is there a link?

Background: Angiopoietin-like protein 4 (Angptl4) is a new circulating protein of the Angiopoietin-like family, predominantly expressed in adipose tissue and liver. A link between Angptl4 and the levels of free fatty acids in human blood plasma remains unclear. Therefore, we hypothesized that any alteration in the concentration of plasma Angptl4 may be mediated by changes in plasma free fatty acid levels in healthy individuals. Methods: To examine the effect of plasma free fatty acid levels on Angptl4 concentrations in humans, ELISA method was developed and used for the quantitative determination of human Angptl4 in plasma samples with known free fatty acid concentrations. Results: It was clearly observed that there were significant (P. value 0.993. Raising plasma fatty acids resulted in an increase in the levels of Angptl4. While, lowering plasma fatty acids resulted in a decrease in the levels of Angptl4. Conclusion: The results of this study indicate that changes in plasma free fatty acid levels are associated with alterations in the concentrations of Angptl4.

Reduction of Methylglyoxal-Induced Glycation by Pyridoxamine Improves Adipose Tissue Microvascular Lesions

Background and Aims. Adipose tissue dysfunction results from many factors, including glycation-induced microvascular damages. We tested the usefulness of inhibiting methylglyoxal-induced glycation to adipose tissue microvasculature in this work, using the antioxidant and dicarbonyl scavenger drug pyridoxamine. Methods. A group of Wistar rats was treated daily with methylglyoxal (MG, 75 mg/Kg/day, 8 weeks). Half of this group was treated with pyridoxamine in the following 4 weeks (Pyr) (100 mg/Kg/day) and the other half did not have any further treatment (MG). A group of Wistar rats without MG treatment was used as control (C). Results. MG group showed decreased HDL cholesterol and increased plasma free fatty acids levels, what was reverted by pyridoxamine. MG also caused an increase of tissue CEL levels (glycation marker), as well as increased staining of PAS and Masson Trichrome-positive components. Pyridoxamine led to CEL and TGF-β levels similar to those observed in control rats and inhibited the accumulation of PAS and Masson Trichrome-positive components. MG caused a decrease of Bcl-2/Bax ratio (marker of apoptosis) and vWF staining (microvascular marker), what was partially reverted by the treatment with pyridoxamine. Conclusions. Preventing methylglyoxal-induced accumulation of glycated and fibrotic materials using pyridoxamine improves the microvascular lesions of the adipose tissue.

Bis(acetylacetonato)-oxovanadium(iv), bis(maltolato)-oxovanadium(iv) and sodium metavanadate induce antilipolytic effects by regulating hormone-sensitive lipase and perilipin via activation of Akt

The increased plasma free fatty acid levels due to the deregulated lipolysis in adipocytes are considered as one of the major risk factors for developing type II diabetes. Vanadium compounds are well-known for their antidiabetic effects both on glucose and lipid metabolism, but the mechanisms are still not completely understood. The present study suggests a mechanism for how vanadium compounds exert antilipolytic effects. It demonstrates that all the three vanadium compounds, bis(acetylacetonato)-oxovanadium(iv) (VO(acac)2), bis(maltolato)-oxovanadium(iv) (VO(ma)2) and sodium metavanadate (NaVO3), attenuated basal lipolysis in 3T3L1 adipocytes in a dose- (from 100 to 400 μM for VO(acac)2 and VO(ma)2, 1.0 to 4.0 mM for vanadate) and time-dependent (from 0.5 to 4 h) manner using the glycerol release as a marker of lipolysis. In addition, the three compounds inhibited lipolysis to a different extent. Among them, VO(acac)2 (from 100 to 400 μM) exerted the most potent effect and reduced the lipolysis to ∼60-20% of control after 4 h treatment. The antilipolytic effects of vanadium compounds were further evidenced by a decrease of the levels of phosphorylated HSL at Ser660 and phosphorylated perilipin, which were counteracted by inhibitors of PI3K or Akt but not by an MEK inhibitor. This indicates that though both Akt and ERK pathways are activated by the vanadium compounds, only Akt activation contributes to the antilipolytic effect of the vanadium compounds, without the involvement of ERK activation. We previously demonstrated that VO(acac)2 can block cell cycle progression at the G1/S phase via a highly activated ERK signal in human hepatoma HepG2 cells. Together with this study, we show that similar activated pathways may lead to differential biological consequences for cancer cells and adipocytes, indicating that vanadium compounds may be used in the prevention and treatment of both diabetes and cancer.

Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n = 10) and in healthy control subjects (n = 67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.

Electroacupuncture and Rosiglitazone Combined Therapy as a Means of Treating Insulin Resistance and Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Aims. To evaluate the efficacy of rosiglitazone (TZD) and electroacupuncture (EA) combined therapy as a treatment for type 2 diabetes mellitus (T2DM) patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N = 15) and the experimental group (TZD + EA, N = 16). Changes in their plasma free fatty acid (FFA), glucose, and insulin levels, together with their homeostasis model assessment (HOMA) indices, were statistically compared before and after treatment. Hypoglycemic activity (%) was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

Dose-dependent effects of diallyl disulfide on plasma glucose and free fatty acid levels in rats

The acute effects of oral administration of diallyl disulfide (DADS), the major organosulfur compound of garlic, on plasma glucose and free fatty acid (FFA) concentrations were examined in rats. Male, 10-week-old Sprague-Dawley rats were divided into DADS-free and DADS-administered (dose = 10, 20, and 40 mg/kg body weight [BW]) groups. Plasma samples were prepared from whole blood drawn from the tail vein 0, 1, 2, 4, and 6 hr after administration. The stomachs were isolated, and the contents were measured 8 hr after administration. In DADS-administered groups, plasma glucose concentrations were increased in a dose-dependent manner 1 hr after the administration. The increase was transient, except in groups administered 40 mg/kg BW of DADS, in which plasma glucose levels remained significantly higher than the DADS-free levels throughout the experimental period. Similar patterns were observed in the plasma FFA concentrations, although the significant differences were lower than those observed in the plasma glucose concentrations. The gastric contents were dose-dependently elevated after DADS administration. The increase was significant when 20 or 40 mg/kg BW of DADS was administered. These results suggest that oral administration of DADS can mobilize energy substrates into the blood, although a higher dose of DADS slows gastric emptying.

Combined Ethanol Extract of Grape Pomace and Omija Fruit Ameliorates Adipogenesis, Hepatic Steatosis, and Inflammation in Diet-Induced Obese Mice

The aim of this study was to evaluate the long-term effects of grape pomace ethanol extract (GPE) with or without omija fruit ethanol extract (OFE) on adiposity, hepatic steatosis, and inflammation in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD) as the control diet and HFD plus GPE (0.5%, w/w) with or without OFE (0.05%, w/w) as the experimental diet for 12 weeks. GPE alone did not significantly affect adipogenesis and hepatic steatosis. However, the supplementation of GPE + OFE significantly lowered body weight gain, white adipose tissue weight, adipocyte size, and plasma free fatty acid and adipokines (leptin, PAI-1, IL-6, and MCP-1) levels in HFD-fed mice compared to those of the control group. These beneficial effects of GPE + OFE were partly related to the decreased expression of lipogenic and inflammatory genes in white adipose tissue. GPE + OFE supplementation also significantly lowered liver weight and ameliorated fatty liver by inhibiting expression of hepatic genes involved in fatty acid and cholesterol syntheses as well as inflammation and by activating hepatic fatty acid oxidation. These findings suggest that the combined ethanol extract of grape pomace and omija fruit has the potential to improve adiposity and fatty liver in diet-induced obese mice.

Particular characteristics of the metabolic syndrome in patients with morbid obesity

BackgroundCriteria for the diagnosis of the metabolic syndrome are currently being reconsidered, as their usefulness is not the same for all phenotypes in relation to the risk of cardiovascular disease. AimWe analyzed the changes in metabolic parameters after a fat overload in different groups of patients. Materials and methodsThe study included 20 healthy persons, 30 metabolic syndrome patients without morbid obesity, 80 metabolic syndrome patients with morbid obesity and 16 patients with morbid obesity without the metabolic syndrome. All the participants received a fat overload of 60g. Measurements were made before the overload and 3h afterwards of triglycerides, free fatty acids, insulin and uric acid. ResultsMetabolic syndrome patients with morbid obesity had a lower waist-to-hip ratio, and lower plasma free fatty acid and triglycerides levels at baseline and after the overload than patients without morbid obesity. Plasma uric acid levels rose after the fat overload in the metabolic syndrome patients who had morbid obesity but not in the patients without morbid obesity. A positive relation was found between plasma triglycerides and free fatty acid levels in all the patients but not in the controls after the fat overload. A positive relation was also found between uric acid and insulin levels in the metabolic syndrome patients with morbid obesity. ConclusionsMetabolic syndrome patients with and without morbid obesity presented different metabolic characteristics. This suggests that there are 2 different clinical phenotypes, both grouped under the metabolic syndrome umbrella.

Palmitic acid increases apoptosis of neural stem cells via activating c-Jun N-terminal kinase

Elevated plasma free fatty acid (FFA) level is common in many pathological conditions, including neurological disorders, and their deleterious effects on various cells have been well documented. However, it remains to be investigated whether elevated FFAs would have a direct effect on neural stem cells (NSCs). Here, we reported that palmitic acid (PA) impaired cell viability and increased apoptosis of NSCs significantly in a dose- and time-dependent manner. Increased protein levels of Bax and cleaved caspase 3 coupled with decreased expression of Bcl-2 were also observed in NSCs with increasing dose or time of PA treatment, whereas caspase 3 expression remained relatively unaltered. In parallel to this, the expression of phospho-c-Jun N-terminal kinase (p-JNK) in NSCs challenged with PA was increased significantly; however, JNK expression appeared stable. Remarkably, JNK inhibitor effectively reduced the apoptosis of NSCs induced by PA. The expression of phospho-p38 (p-p38), p38, phospho-extracellular regulated protein kinases 1/2 (p-EKR1/2) and EKR1/2 in NSCs was not affected by PA treatment. In consideration of the above, it is suggested that elevated plasma FFA level may induce apoptosis of NSCs in vivo, and that this might be one of possible underlying mechanisms for the cognitive disturbance in neurological disorders.

Tyk2 and Stat3 Regulate Brown Adipose Tissue Differentiation and Obesity

Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2(-/-) brown preadipocytes. Furthermore, Tyk2(-/-) mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans.