1-trifluoromethoxyphenyl-3(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor attenuates high fat diet-induced cardiovascular and metabolic disorders in rats.

OBJECTIVE: Obesity was induced in rats by feeding on a high fat diet (HFD), 60% w/w cholesterol, 20% w/w carbohydrates, and 20% w/w proteins for two months. MATERIALS AND METHODS: Animals were fed on a HFD and treated concurrently with a single daily dose of vehicle or TPPU (2 mg/kg p.o) for two months. Body weights, blood pressure, and biochemical investigations of all animals were registered at 0, 1, and 2 months of the experimental period. RESULTS: Vehicle-treated rats fed on a HFD had a considerable increase in body weight compared to age-matched control animals fed on a regular diet (regular diet; 311.40 ±9.60 vs. HFD; 446 ± 12.67). The body weight of rats fed on a HFD and concurrently treated with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4yl) urea (TPPU; 2 mg/kg p.o) daily for two months was significantly decreased (p<0.01). A significant (p<0.01) increase in the systolic blood pressure of animals and vascular dysfunction with blunted relaxant response to acetylcholine and sodium nitroprusside was evident in vehicle-treated animals fed on a HFD compared to control rats fed on a regular diet. These HFD-induced disorders were markedly attenuated in animals fed on a HFD and treated concurrently with a single daily dose of TPPU (2 mg/kg p.o). HFD diet-induced deleterious metabolic changes were prevented with concurrent administration of TPPU (2 mg/kg p.o). TPPU treatment decreased the HDF-induced increase in plasma creatinine levels (p<0.001) in rats. The adiponectin levels were decreased (p<0.001) in vehicle-treated rats fed on HFD for two months compared to control rats fed on a normal diet (p<0.001). Adiponectin levels were significantly (p<0.001) increased in rats fed on HFD and treated concurrently with TPPU (2 mg/kg p.o). HFD diet caused a marked increase in plasma leptin levels of animals which were significantly decreased in animals fed on a HFD and treated concurrently with TPPU for two months. Obese animals exhibited increased levels of plasma insulin compared to control animals fed on a regular diet which were significantly suppressed (p<0.001) by TPPU treatment. In the current investigation, TPPU treatment had a favorable impact on the levels of other metabolic parameters such as plasma cholesterol, triglycerides (TGs), low density lipoproteins (LDLs), and high density lipoproteins (HDL). HFD caused a profound increase in the serum liver enzymes, the effect was reversed by treatment of animals with TPPU (2 mg/kg p.o). CONCLUSIONS: The findings of our current study indicate the promising therapeutic potential of TPPU as a new drug candidate to manage obesity-induced cardiovascular and metabolic disorders. Soluble epoxide hydrolase inhibitors such as TPPU could prevent HFD-induced obesity and related cardiovascular and metabolic complications.

The saudi clinical practice guideline for the management of overweight and obesity in adults

OBJECTIVE: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. METHODS: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence. RESULTS: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults. These included strong recommendations in support of lifestyle interventions rather than usual care alone, individualized counseling interventions rather than generic educational pamphlets, physical activity rather than no physical activity, and physical activity in addition to diet rather than diet alone. Metformin and orlistat were suggested as conditional recommendations for the management of overweight and obesity in adults. Bariatric surgery was recommended, conditionally, for the management of obese adults (body mass index of ≥40 or ≥35 kg/m2 with comorbidities). CONCLUSIONS: The current guideline includes recommendation for the non-pharmacological, pharmacological, and surgical management of overweight and obese adults. In addition, the panel recommends conducting research priorities regarding lifestyle interventions and economic analysis of drug therapy within the Saudi context, as well as long term benefits and harms of bariatric surgery.

Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population.

Recent genome wide association studies identified many loci in several genes that have been consistently associated with type 2 diabetes mellitus in various ethnic populations. Among the genes that were most strongly associated with diabetes were fat mass- and obesity-associated, melanocortin 4 receptor, solute carrier family 30 member 8 (SLC30A8), and a member of the potassium voltage-gated channels. In the present study, we examined the association between variants in fat mass- and obesity-associated [rs9939609 (A/T)], melanocortin 4 receptor [rs17782313 (C/T), and rs12970134 (A/G)], SLC30A8 [rs13266634 (C/T)], and a member of the potassium voltage-gated channels [rs2237892(C/T)] genes in diabetes patients from Saudi Arabia. Genotypes were determined using the TaqMan single-nucleotide polymorphism genotype analysis technique. Minor allele frequency of the 4 variants tested was comparable between type 2 diabetes cases and controls. We observed an association between allele variants of SLC30A8 [rs13266634 (C/T)] and type 2-diabetes (P = 0.04). The other single-nucleotide polymorphisms examined in this study showed moderate or no correlation with diabetes in Saudis. Our data indicate that the SLC30A8 polymorphisms are associated with type 2 diabetes in the Saudi population. There is no evidence supporting an association between variants in the fat mass- and obesity-associated and melanocortin 4 receptor, and a member of the potassium voltage-gated channels genes and type 2 diabetes in the Saudi population.

Eosinophilic colitis is a sporadic self-limited disease of middle-aged people: a population-based study.

AIM: Eosinophilic colitis (EC) is a rare manifestation of eosinophilic gastrointestinal disorders. Due to its rarity, little information is available on its natural history. METHOD: From the single population-based pathology database of the Calgary Health Region (comprising a population of 1.28 million in 2008), cases of EC during the period 1996-2008 were identified. Medical records of all adults diagnosed with EC were identified and the pathology reviewed. The patients were then contacted for follow-up using a standardized questionnaire. RESULTS: Seven cases of EC (four in women) were identified, with a median follow-up of 45 (23-79) months. The median age at diagnosis was 42 (22-70) years. Symptoms at diagnosis were abdominal pain (86%), nonbloody diarrhoea (57%), bloody diarrhoea (29%) and significant (>10%) weight loss (29%). Three patients gave a history of allergic reactions to drugs and four reported allergy to cows' milk. Endoscopic findings were nonspecific, ranging from oedema to small aphthous ulceration. An eosinophilic infiltrate was identified in the lamina propria in the initial colonic biopsy in all patients. Over the longer term, three patients experienced spontaneous resolution without treatment. Two continued to have mild diarrhoea and abdominal cramps but did not require medical therapy. Two patients required medical treatment by 5-aminosalicylic acid, with one requiring prednisone and azathioprine maintenance therapy. CONCLUSION: Eosinophilic colitis is a rare mostly self-limiting disease affecting middle-aged adults. It usually has a mild clinical course and drug treatment is not usually necessary. When required, drug treatment follows the standard medication for other inflammatory bowel disease.

Use of MRI and CT for fat imaging in children and youth: what have we learned about obesity, fat distribution and metabolic disease risk?

Childhood obesity is a matter of great concern for public health. Efforts have been made to understand its impact on health through advanced imaging techniques. An increasing number of studies focus on fat distribution and its associations with metabolic risk, in interaction with genetics, environment and ethnicity, in children. The present review is a qualitative synthesis of the existing literature on visceral and subcutaneous abdominal, intrahepatic and intramuscular fat. Our search revealed 80 original articles. Abdominal as well as ectopic fat depots are prevalent already in childhood and contribute to abnormal metabolic parameters, starting early in life. Visceral, hepatic and intramuscular fat seem to be interrelated but their patterns as well as their independent contribution on metabolic risk are not clear. Some ethnic-specific characteristics are also prevalent. These results encourage further research in childhood obesity by using imaging techniques such as magnetic resonance imaging and computed tomography. These imaging methods can provide a better understanding of fat distribution and its relationships with metabolic risk, compared to less detailed fat and obesity assessment. However, studies on bigger samples and with a prospective character are warranted.

Blood thiamine and its phosphate esters as measured by high-performance liquid chromatography: levels and associations in diabetes mellitus patients with varying degrees of microalbuminuria.

BACKGROUND: Thiamine deficiency has been linked to microvascular complications in patients with diabetes mellitus (DM). In this study, we aim to assess blood and urine thiamine status by high performance liquid chromatography (HPLC) in patients with DM Type 1 and Type 2 (DMT1, DMT2) and to identify associations with markers of incipient nephropathy and kidney dysfunction. SUBJECTS AND METHODS: A total of 205 subjects (43 DMT1 and 162 DMT2) with and without microalbuminuria and 26 non-diabetic controls were included. Fasting blood samples were collected and anthropometric parameters were measured. Fasting blood, lipid and renal profile were determined routinely. Blood thiamine concentration, its phosphate esters and urine thiamine were quantified using HPLC. RESULTS: Blood thiamine concentrations (ng 1-1) were decreased by 75.7% and 49.6% in patients with DMT1 and DMT2, respectively [controls (54.8+/-11.4); DMT1 (41.5+/-17.9); DMT2 (27.2+/-12.7), p<0.001]. Among those with normo-albuminuria, urinary excretion of thiamine was significantly increased to 390.1 microg/ml and 1212.4 microg/ml in DMT1 and DMT2 respectively, as compared to controls (326.4 microg/ml). DMT1 and DMT2 patients with micro- albuminuria on the other hand had 2.5- and 3.4-fold increase in urinary excretion of thiamine compared to controls. CONCLUSION: Low levels of blood thiamine are present in patients with DMT1 and DMT2, and are associated with increased thiamine clearance.