Inhibition of the Renin-Angiotensin System Reduces Gene Expression of Inflammatory Mediators in Adipose Tissue Independent of Energy Balance.

Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.

Neural Function Before and After Mindfulness-Based Cognitive Therapy in Anxious Adolescents at Risk for Developing Bipolar Disorder.

OBJECTIVE: We sought to evaluate the neurophysiology of mindfulness-based cognitive therapy for children (MBCT-C) in youth with generalized, social, and/or separation anxiety disorder who were at risk for developing bipolar disorder. METHODS: Nine youth (mean age: 13 ± 2 years) with a generalized, social, and/or separation anxiety disorder and a parent with bipolar disorder completed functional magnetic resonance imaging (fMRI) while performing a continuous processing task with emotional and neutral distractors (CPT-END) prior to and following 12 weeks of MBCT-C. RESULTS: MBCT-C was associated with increases in activation of the bilateral insula, lentiform nucleus, and thalamus, as well as the left anterior cingulate while viewing emotional stimuli during the CPT-END, and decreases in anxiety were correlated with change in activation in the bilateral insula and anterior cingulate during the viewing of emotional stimuli (p < 0.05, uncorrected; p < 0.005 corrected; cluster size, 37 voxels). CONCLUSIONS: MBCT-C treatment in anxious youth with a familial history of bipolar disorder is associated with increased activation of brain structures that subserve interoception and the processing of internal stimuli-functions that are ostensibly improved by this treatment.

Hypertension induced by omega-3 polyunsaturated fatty acid deficiency is alleviated by alpha-linolenic acid regardless of dietary source.

Omega-3 polyunsaturated fatty acid deficiency, particularly during the prenatal period, can cause hypertension in later life. This study examined the effect of different sources of alpha-linolenic acid (canola oil or flaxseed oil) in the prevention of hypertension and other metabolic symptoms induced by an omega-3 fatty acid-deficient diet. Dams were provided one of three experimental diets from 1 week before mating. Diets were either deficient (10% safflower oil-DEF) or sufficient (7% safflower oil+3% flaxseed oil-SUF-F; or 10% canola oil-SUF-C) in omega-3 fatty acids. The male offspring were continued on the maternal diet from weaning for the duration of the study. Body weight, ingestive behaviors, blood pressure, body composition, metabolic rate, plasma leptin and brain fatty acids were all assessed. The DEF animals were hypertensive at 24 weeks of age compared with SUF-F or SUF-C animals; this was not evident at 12 weeks. These results suggest that different sources of ALA are effective in preventing hypertension related to omega-3 fatty acid deficiency. However, there were other marked differences between the DEF and, in particular, the SUF-C phenotype including lowered body weight, adiposity, leptin and food intake in SUF-C animals. SUF-F animals also had lower, but less marked reductions in adiposity and leptin compared with DEF animals. The differences observed between DEF, SUF-F and SUF-C phenotypes indicate that body fat and leptin may be involved in omega-3 fatty acid deficiency hypertension.

Dietary protein level interacts with omega-3 polyunsaturated fatty acid deficiency to induce hypertension.

BACKGROUND: Dietary omega-3 fatty acid deficiency can lead to hypertension in later life; however, hypertension is affected by numerous other dietary factors. We examined the effect of altering the dietary protein level on blood pressure in animals deficient or sufficient in omega-3 fatty acids. METHODS: Female rats were placed on one of four experimental diets 1 week prior to mating. Diets were either deficient (10% safflower oil; DEF) or sufficient (7% safflower oil, 3% flaxseed oil; SUF) in omega-3 fatty acids and contained 20 or 30% casein (DEF20, SUF20, DEF30, SUF30). Offspring were maintained on the maternal diet for the duration of the experiment. At 12, 18, 24, and 30 weeks, blood pressure was assessed by tail cuff plethysmography. RESULTS: At both 12 and 18 weeks of age, no differences in blood pressure were observed based on diet, however, by 24 weeks hypertension was evident in DEF30 animals; there were no blood pressure differences between the other groups. This hypertension in DEF30 group was increased at 30 weeks, with systolic, diastolic, and mean arterial pressure all elevated. CONCLUSIONS: These results indicate that the hypertension previously attributed to omega-3 fatty acid deficiency is dependent on additional dietary factors, including protein content. Furthermore, this study is the first to plot the establishment of omega-3 fatty acid deficiency hypertension over time.

The role of omega-3 fatty acids in mood disorders.

Research has established that docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), plays a fundamental role in brain structure and function. Epidemiological and cross-sectional studies have also identified a role for long-chain omega-3 PUFA, which includes DHA, eicosapentaenoic acid, and docosapentaenoic acid, in the etiology of depression. In the past ten years, there have been 12 intervention studies conducted using various preparations of longchain omega-3 PUFA in unipolar and bipolar depression. The majority of these studies administered long-chain omega-3 PUFA as an adjunct therapy. The studies have been conducted over 4 to 16 weeks of intervention and have often included small cohorts. In four out of the seven studies conducted in depressed individuals and in two out of the five studies in bipolar patients, individuals have reported a positive outcome following supplementation with ethyl-eicosapentaenoic acid or fish oil containing long-chain omega-3 PUFA. In the three trials that researched the influence of DHA-rich preparations, no significant effects were reported. The mechanisms that have been invoked to account for the benefits of long-chain omega-3 PUFA in depression include reductions in prostaglandins derived from arachidonic acid, which lead to decreased brain-derived neurotrophic factor levels and/or alterations in blood flow to the brain.