Role of cytochrome P450-derived, polyunsaturated fatty acid mediators in diabetes and the metabolic syndrome

Results of the study related to polymorphism of ACE gene (rs1799752)‎, integrin αIIbβ3, and CSK gene (rs1378942) influencing development of arterial hypertension in young patients with metabolic syndrome are presented. Hypertension as a component of the metabolic syndrome was detected in 15.0% of young patients. Prevalence of mutant alleles of the studied genes among the examined patients was quite high, so homozygous DD genotype was found in 21.6%, and mutant D allele of the ACE gene in 47.4%. A high risk of hypertension in patients with MS was detected in carriers of the T allele of the CSK (rs1378942) gene – 54.8%, which was most often observed in a combination of polymorphic ACE and CSK gene loci (p = 0.0053).

Download Full-text

Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors

Journal of Clinical Medicine ◽

10.3390/jcm10081567 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1567

Author(s):

Katarzyna Konończuk ◽

Eryk Latoch ◽

Beata Żelazowska-Rutkowska ◽

Maryna Krawczuk-Rybak ◽

Katarzyna Muszyńska-Rosłan

Keyword(s):

Metabolic Syndrome ◽

Fatty Acid ◽

Acute Lymphoblastic Leukemia ◽

Binding Proteins ◽

Lymphoblastic Leukemia ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Significant Difference

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

Download Full-text

The Role of Quinapril in the Presence of a Weight Loss Regimen: Endothelial Function and Markers of Obesity in Patients With the Metabolic Syndrome

Preventive Cardiology ◽

10.1111/j.1520-037x.2007.06556.x ◽

2007 ◽

Vol 10 (4) ◽

pp. 204-209 ◽

Cited By ~ 10

Author(s):

Sameer Nagamia ◽

Anbu Pandian ◽

Faiz Cheema ◽

Rama Natarajan ◽

Qamar A. Khan ◽

...

Keyword(s):

Metabolic Syndrome ◽

Weight Loss ◽

Endothelial Function ◽

The Metabolic Syndrome

Download Full-text

Dietary lipids and gene expression

Biochemical Society Transactions ◽

10.1042/bst0320999 ◽

2004 ◽

Vol 32 (6) ◽

pp. 999-1002 ◽

Cited By ~ 24

Author(s):

H.M. Roche

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Transcription Factors ◽

Fatty Acid ◽

Regulatory Element ◽

Nuclear Factor Κb ◽

Dietary Lipids ◽

Dietary Fatty Acids ◽

Dietary Fatty Acid ◽

The Metabolic Syndrome

Nutrition is a key environmental factor that is particularly involved in the pathogenesis and progression of several polygenic, diet-related diseases. Nutrigenomics refers to the interaction between nutrition and the human genome. Dietary fatty acids interact with multiple nutrient-sensitive transcription factors. This explains the molecular basis of some of the health effects associated with altered dietary fatty acid composition. The metabolic syndrome is a very common condition, characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and is associated with a greater risk of cardiovascular disease. Several lines of evidence suggest that the interaction between nutrient-derived metabolic stressors and pro-inflammatory signals play an important role in the aetiology of insulin resistance and the development of the metabolic syndrome. This paper will address the interaction between several nutrient-sensitive transcription factors, including SREBP (sterol-regulatory-element-binding protein) and NFκB (nuclear factor κB), demonstrating how this interaction may be altered with dietary fatty acid interventions.

Download Full-text

The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome

The Journal of Clinical Pharmacology ◽

10.1177/0091270007299358 ◽

2007 ◽

Vol 47 (5) ◽

pp. 642-652 ◽

Cited By ~ 35

Author(s):

Anna I. Kakafika ◽

Dimitri P. Mikhailidis ◽

Asterios Karagiannis ◽

Vasilios G. Athyros

Keyword(s):

Metabolic Syndrome ◽

Endocannabinoid System ◽

The Metabolic Syndrome

Download Full-text

Enhanced phosphorylation of Na+–Cl− co-transporter in experimental metabolic syndrome: role of insulin

Clinical Science ◽

10.1042/cs20120003 ◽

2012 ◽

Vol 123 (11) ◽

pp. 635-647 ◽

Cited By ~ 38

Author(s):

Radko Komers ◽

Shaunessy Rogers ◽

Terry T. Oyama ◽

Bei Xu ◽

Chao-Ling Yang ◽

...

Keyword(s):

Metabolic Syndrome ◽

Time Course ◽

Kinase Inhibitor ◽

Endogenous Expression ◽

The Metabolic Syndrome ◽

Mammalian Cell Lines ◽

Phosphoinositide 3 Kinase

In the present study, we investigated the activity of the thiazide-sensitive NCC (Na+–Cl− co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr53 NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.

Download Full-text