Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFA) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) have shown beneficial effects on learning and memory, neuroinflammatory processes and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-archidonoylglycerol (2-AG) are the most widely studied endocannabinoids, and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair

Lack of Benefit of Early Intervention with Dietary Flax and Fish Oil and Soy Protein in Orthologous Rodent Models of Human Hereditary Polycystic Kidney Disease

<div><p>Rationale for dietary advice in polycystic kidney disease (PKD) is based in part on animal studies that have examined non-orthologous models with progressive development of cystic disease. Since no model completely mimics human PKD, the purpose of the current studies was to examine the effects of dietary soy protein (compared to casein) or oils enriched in omega-3 fatty acids (fish or flax oil compared to soy oil) on early disease progression in two orthologous models of PKD. The models studied were <i>Pkd2</i>^WS25/- mice as a model of autosomal dominant PKD, and PCK rats as a model of autosomal recessive PKD. After 13 weeks of feeding, dietary fish (but not flax) oil resulted in larger kidneys and greater kidney water content in female <i>Pkd2</i>^WS25/- compared to control mice. After 12 weeks of feeding male PCK compared to control rats, both fish and flax compared to soy oil resulted in enlarged kidneys and livers, greater kidney water content and higher kidney cyst area in diseased rats. Dietary soy protein compared to casein had no effects in <i>Pkd2</i>^WS25/- compared to control mice. In PCK rats, kidney and liver histology were not improved, but lower proteinuria and higher urine pH suggest that soy protein could be beneficial in the long term. Therefore, in contrast to studies in non-orthologous models during the progressive development phase, these studies in orthologous PKD models do not support dietary advice to increase soy protein or oils enriched in omega-3 oils in early PKD.</p></div

Disease effects in male PCK rats.

<p>Disease effects in male PCK rats.</p

Disease and sex effects in <i>Pkd2</i>^WS25/- and <i>Pkd2</i>^WS25/+ mice.

<p>Disease and sex effects in <i>Pkd2</i>^WS25/- and <i>Pkd2</i>^WS25/+ mice.</p

Kidney sections.

<p>Sections A-D are from Pkd2 mice and E-F are from PCK rats as follows: (A) <i>Pkd2</i>^WS25/+ (normal) and (B) <i>Pkd2</i>^WS25/- (diseased) mice provided soy oil, <i>Pkd2</i>^WS25/- (diseased) mice provided (C) flax oil or (D) fish oil, (E) normal and (F) PCK rats provided soy oil, PCK rats provided (G) flax oil or (H) fish oil. Scale bar = 1 mm.</p

Dietary oil and protein effects in diseased PCK rats.

<p>Dietary oil and protein effects in diseased PCK rats.</p

Physical activity and cardiometabolic health in adolescents with type 2 diabetes: a cross-sectional study

Introduction Youth living with type 2 diabetes display increased risk of cardiovascular disease (CVD). It is unclear if regular physical activity (PA) modifies this risk.Research design and methods We compared CVD risk factors in a cross-sectional study of 164 youth with type 2 diabetes stratified according to weekly vigorous-intensity PA. Outcomes were hemoglobin A1c (HbA1c), ambulatory blood pressure (BP; ambulatory 24-hour readings), plasma lipoproteins, and albuminuria. The main exposure, vigorous-intensity PA, was quantified with the Adolescent Physical Activity Recall Questionnaire.Results Youth were 15±3 years, and 78% lived rurally and 68% were female, with a mean body mass index (BMI) Z-score of 2.4±1.1 and a mean HbA1c of 9.6% ±2.6%. Youth who participated in regular vigorous-intensity PA (40%; n=67) achieved nearly twice the dose of PA than peers who did not (62 vs 34 metabolic equivalent score-hour/week, p=0.001). After adjusting for duration of diabetes, BMI Z-score, sex, and smoking, youth who engaged in vigorous-intensity PA displayed lower HbA1c (9.1% vs 9.9%, p=0.052), diastolic BP (70 mm Hg vs 73 mm Hg, p=0.002), diastolic load (20% vs 26%, p=0.023), and mean arterial pressure (87.3 mm Hg vs 90.3 mm Hg, p&lt;0.01), compared with youth who did not. Compared with youth who did not participate in regular vigorous-intensity PA, those who did also displayed lower odds of albuminuria after adjusting for duration of diabetes, sex, smoking, rural residence, and BMI Z-score (adjusted OR: 0.40, 95% CI 0.19 to 0.84).Conclusions Among youth with type 2 diabetes, participation in vigorous-intensity PA is associated with lower CVD risk

Liver sections.

<p>Sections A-D are from Pkd2 mice and E-F are from PCK rats as follows: (A) <i>Pkd2</i>^WS25/+ (normal) and (B) <i>Pkd2</i>^WS25/- (diseased) mice provided soy oil, <i>Pkd2</i>^WS25/- (diseased) mice provided (C) flax oil or (D) fish oil, (E) normal and (F) PCK rats provided soy oil, PCK rats provided (G) flax oil or (H) fish oil. Scale bar = 1 mm.</p