Gestational hyperlipidemia in the rat is characterized by accumulation of n - 6 and n - 3 fatty acids, especially docosahexaenoic acid.

We have evaluated the relative and quantitative changes in long-chain fatty acids in maternal liver, serum, carcass and conceptus (fetuses plus placentae) during pregnancy in the rat, to ascertain whether previous concern over lower proportions of n - 6 and n - 3 fatty acids in maternal serum could be indicative of suboptimal n - 6 or n - 3 fatty acid status. Gestational hyperlipidemia was characterized by proportional decreases in linoleic, stearic and arachidonic acids but increases in palmitic and docosahexaenoic acids. However, the quantitative amount (microgram/ml) of linoleic, arachidonic and docosahexaenoic acids in serum lipids actually increased 2-5-fold from mid-pregnancy to term. Compared to non-pregnant rats, gestational hyperlipidemia was also associated with a lower proportion but similar quantity of linoleic acid in maternal carcass and adipose stores. We conclude that gestational hyperlipidemia in the rat is characterized by a relative but not quantitative decrease in whole-body stores of n - 6 fatty acids and a marked proportional and quantitative increase in docosahexaenoic acid in maternal organs and in the conceptus.     

Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet

The effect of long-term calorie restriction (CR) on metabolites, fatty acid profiles and energy substrate transporter expression in the brain was assessed in aged rats. Three groups of male Sprague–Dawley rats were studied: (i) a 2 month old ad libitum-fed (2AL group), (ii) a 19 month old ad libitum-fed (19AL group), and (iii) a 19 month old group subjected to 40% CR from the age of 7.5 to 19 months (19CR group). The diet contained high sucrose and low n-3 polyunsaturated fatty acids (PUFA) so as to imitate a Western-style diet. High resolution magic angle spinning-¹H NMR showed an effect of aging on brain cortex metabolites compared to 2AL rats, the largest differences being for myo-inositol (+251% and +181%), lactate (+203% and +188%), β-hydroxybutyrate (+176% and +618%) and choline (+148% and +120%), in 19AL and 19 CR rats, respectively. However, brain metabolites did not differ between the 19AL and 19CR groups. Cortex fatty acid profiles showed that n-3 PUFA were 35–47% lower but monounsaturated fatty acids were 40–52% higher in 19AL and 19CR rats compared to 2AL rats. Brain microvessel glucose transporter (GLUT1) was 68% higher in 19AL rats than in 2AL rats, while the monocarboxylate transporter, MCT1, was 61% lower in 19CR rats compared to 19AL rats. We conclude that on a high-sucrose, low n-3 PUFA diet, the brain of aged AL rats had higher metabolites and microvessel GLUT1 expression compared to 2AL rats. However, long-term CR in aged rats did not markedly change brain metabolite or fatty acid profile, but did reduce brain microvessel MCT1 expression.     

Survival of the fattest: fat babies were the key to evolution of the large human brain

In the past 2 million years, the hominid lineage leading to modern humans evolved significantly larger and more sophisticated brains than other primates. We propose that the modern human brain was a product of having first evolved fat babies. Hence, the fattest (infants) became, mentally, the fittest adults. Human babies have brains and body fat each contributing to 11-14% of body weight, a situation which appears to be unique amongst terrestrial animals. Body fat in human babies provides three forms of insurance for brain development that are not available to other land-based species: (1) a large fuel store in the form of fatty acids in triglycerides; (2) the fatty acid precursors to ketone bodies which are key substrates for brain lipid synthesis; and (3) a store of long chain polyunsaturated fatty acids, particularly docosahexaenoic acid, needed for normal brain development. The triple combination of high fuel demands, inability to import cholesterol or saturated fatty acids, and dependence on docosahexaenoic acid puts the mammalian brain in a uniquely difficult situation compared with other organs and makes its expansion in early humans all the more remarkable. We believe that fresh- and salt-water shorelines provided a uniquely rich, abundant and accessible food supply, and the only viable environment for evolving both body fat and larger brains in human infants.     

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance

Objective

To investigate whether cerebral metabolic rate of glucose (CMR_glu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance.

Materials and methods

Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function.

Results

The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9–14% lower CMR_glu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMR_glu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.

Conclusions

The PCOS group exhibited a pattern of low regional CMR_glu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer’s disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.     

Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

Background

Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.

Methods

Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.

Results

Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.

Conclusions

Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.

     

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

Background  

Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.     

Protein structure similarity from principle component correlation analysis

Background  

Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities.