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 (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group).

Impaired Fluid Intake, but Not Sodium Appetite, in Aged Rats Is Mediated by the Cyclooxygenase-Prostaglandin E Pathway.

Aging results in decreased fluid intake following dehydration and other dipsogenic stimuli; similar reductions in sodium intake have also been observed with aging. Given that cyclooxygenase (COX)-derived prostanoids are elevated in aged rats in the midbrain and proinflammatory prostanoids are known to decrease fluid intake in dehydrated rats, the aim of this study was to determine if the reductions of fluid intake and sodium intake in aging are mediated by proinflammatory eicosanoid signaling. Therefore, we examined the effect of acute COX inhibition in adult (4 months-old) and aged (30 months-old) rats prior to ingestive behavior challenges.

Dietary repletion with ω3 fatty acid or with COX inhibition reverses cognitive effects in F3 ω3 fatty-acid-deficient mice.

Dietary deficiency of ω3 fatty acid during development leads to impaired cognitive function. However, the effects of multiple generations of ω3 fatty-acid deficiency on cognitive impairment remain unclear. In addition, we sought to test the hypothesis that the cognitive impairments of ω3 fatty-acid-deficient mice are mediated through the arachidonic acid-cyclooxygenase (COX) pathway.

Reductions in water and sodium intake by aged male and female rats.

Aging results in reduced water and sodium intake responses in male rats. Because sex differences exist for water and sodium ingestion of young adult animals, we hypothesized that these sex differences would protect against the diminished water and sodium ingestion of aged female rats. Water and sodium intakes were examined in male and female young adult and aged Brown Norway rats in response to dipsogenic stimuli.

Calorie restricted rats do not increase metabolic rate post-LPS, but do seek out warmer ambient temperatures to behaviourally induce a fever.

Due to previous work where we have demonstrated attenuated febrile responses post-lipopolysaccharide (LPS) in calorie restricted (CR) rodents we aimed to explore metabolic rate and behavioral thermoregulation in these CR animals post-LPS. Male Sprague-Dawley rats fed ad libitum (AL) or restricted to 50% (CR50%) of the AL animals' food intake for 28 days were injected on the 29th day with 50 μg/kg of LPS. Core body temperature (T(b)), self-selected self-selected ambient temperature (T(a)), indirect calorimetry [to determine energy expenditure (EE) and respiratory quotient (RQ)] were measured in AL and CR animals for 8 hours post-LPS.

Thirst deficits in aged rats are reversed by dietary omega-3 fatty acid supplementation.

During heat waves many elderly individuals die as a consequence of dehydration. This is partially due to deficits in mechanisms controlling thirst. Reduced thirst following dipsogenic stimuli is well documented in aged humans and rodents.

Hypothalamic gene expression in ω-3 PUFA-deficient male rats before, and following, development of hypertension.

Dietary deficiency of ω-3 fatty acids (ω-3 DEF) produces hypertension in later life. This study examined the effect of ω-3 DEF on blood pressure and hypothalamic gene expression in young rats, before the development of hypertension, and in older rats following the onset of hypertension. Animals were fed experimental diets that were deficient in ω-3 fatty acids, sufficient in short-chain ω-3 fatty acids or sufficient in short- and long-chain ω-3 fatty acids, from the prenatal period until 10 or 36 weeks-of-age.

The role of angiotensin in obesity and metabolic disease.

Obesity is associated with increased body fat composition and elevated risk of metabolic and cardiovascular disease. The activity of the renin-angiotensin system is generally increased in obesity and experimental evidence has shown that angiotensin influences appetite and metabolism as well as mechanisms that induce adipose tissue growth and metabolism in peripheral organs. This review summarises some of the key evidence from animal and human experiments that links the renin-angiotensin system to obesity and metabolic disease.

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.

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet.

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water.

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.

Antagonists of the renin-angiotensin system and the prevention of obesity.

In addition to its role as an energy store, adipose tissue also acts as an endocrine organ, synthesizing and secreting hormones and cytokines. This review discusses angiotensin II (Ang-II), the biologically active component of the renin-angiotensin system (RAS). Evidence suggests that a functioning RAS is present in adipose tissue.

Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet.

The renin-angiotensin system (RAS) is functional within adipose tissue and angiotensin II, the active component of RAS, has been implicated in adipose tissue hypertrophy and insulin resistance. In this study, captopril, an angiotensin converting enzyme (ACE) inhibitor that prevents angiotensin II formation, was used to study the development of diet-induced obesity and insulin resistance in obesity prone C57BL/6J mice. The mice were fed a high fat diet (w/w 21% fat) and allowed access to either water or water with captopril added (0.

The role of eicosanoids in the brain.

The brain contains two main polyunsaturated fatty acids (PUFA), arachidonic acid (AA) and docosahexaenoic acid (DHA). These PUFA are located almost exclusively in the sn2-position of phosphoglycerides which are found in the neural cell membranes. Liberation of these PUFA from the phosphoglycerides occurs via the action of specific phospholipases (PLA2).

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance.

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE(-/-)) and compared with wild-type littermates.

Angiotensin converting enzyme inhibition from birth reduces body weight and body fat in Sprague-Dawley rats.

In vitro studies have demonstrated that angiotensin II (ANG II) induces adipocyte hyperplasia and hypertrophy. The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibition on body weight, adiposity and blood pressure in Sprague-Dawley rats. From birth half of the animals (n=15) were given water to drink, while the remainder were administered perindopril in their drinking water (2 mg/kg/day).

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.

Omega 3 fatty acids and the brain: review of studies in depression.

The brain is a lipid-rich organ containing mostly complex polar phospholipids, sphingolipids, gangliosides and cholesterol. These lipids are involved in the structure and function of cell membranes in the brain. The glycerophospholipids in the brain contain a high proportion of polyunsaturated fatty acids (PUFA) derived from the essential fatty acids, linoleic acid and alpha-linolenic acid.

The problem of obesity: is there a role for antagonists of the renin-angiotensin system?

Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin II (ANG II) is the biologically active component of the renin-angiotensin system (RAS).

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion.

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e.

Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease.

Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

Objective: To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling.

Research Methods And Procedures: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning.

Attenuation of scopolamine-induced learning deficits by LVV-hemorphin-7 in rats in the passive avoidance and water maze paradigms.

Central administration of angiotensin IV (Ang IV) analogues attenuates scopolamine-induced amnesia. Ang IV mediates its effects by binding to a high affinity, binding site, AT(4) receptor, that has recently been identified as insulin regulated aminopeptidase (IRAP). The purpose of this study was to examine the effect of the distinct AT(4) ligand, LVV-hemorphin-7 (LVV-H7), on scopolamine-induced learning deficits, one which involves fear-conditioning and the other spatial learning.

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression.

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats.

Increased blood pressure later in life may be associated with perinatal n-3 fatty acid deficiency.

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n-3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n-3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control.