Caloric Restriction Alters the Metabolic Response to a Mixed-Meal: Results from a Randomized, Controlled Trial

OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion

The Fibroblast Specific α11β1 Integrin is Important for Postnatal Cardiomyocyte Growth, Alignment and Function

Integrins are transmembrane adhesion and signaling receptors that interact with the extracellular matrix to mediate diverse cellular and developmental processes. Recent work has demonstrated cardiac fibroblasts mediate cardiomyocyte development through integrins. However, the predominant integrins involved and the role of integrins in cardiac development is poorly defined. Thus, we investigated the contribution of the α11β1 integrin (α11), which is expressed by fibroblasts and binds preferentially to type I collagen fibers, in mediating postnatal cardiomyocyte development and function. Utilizing a germline mutation of the α11 gene in mice, we found that deletion resulted in growth and structural abnormalities in cardiomyocyte development and reductions in myocardial collagen, which was associated with impairments in both active and passive diastolic function. These results suggest that the α11 integrin is a key component of the cardiac fibroblast that is required for the normal development of cardiomyocytes and maintenance of cardiac function.M.Sc.2016-11-24 00:00:0

Physical oceaongraphy and hydrochemistry measured on water bottle samples during METEOR cruise M84/3 in 2001

Here we report on data from an oceanographic cruise on the German research vessel Meteor covering large parts of the Mediterranean Sea during spring of 2011. The main objective of this cruise was to conduct measurements of physical, chemical and biological variables on a section across the Mediterranean Sea with the goal of producing a synoptic picture of the distribution of relevant physical and biogeochemical properties, in order to compare those to historic data sets. During the cruise, a comprehensive data set of relevant variables following the guide lines for repeat hydrography outlined by the GO-SHIP group (http://www.go-ship.org/) was collected. The measurements include salinity and temperature (CTD), an over-determined carbonate system, inorganic nutrients, oxygen, transient tracers (CFC-12, SF6), helium isotopes and tritium, and carbon isotopes. The cruise sampled all major basins of the Mediterranean Sea following roughly an east-to-west section from the coast of Lebanon through to the Strait of Gibraltar, and to the coast of Portugal. Also a south-to-north section from the Ionian Sea to the Adriatic Sea was carried out. Additionally, sampling in the Aegean, Adriatic and Tyrrhenian Seas were carried out. The sections roughly followed lines and positions that have been sampled previously during other programs, thus providing the opportunity for comparative investigations of the temporal development of various parameters

Addressing the need for a new generation of young translational researchers that focuses on societal impact: The Apollo Toronto Story

Translational research (TR) is a multidirectional and multidisciplinary integration of basic research, patient-oriented research and population-based research, with the long-term goal of improving human health. Unfortunately, the current scientific training system does not adequately align with the goals of TR. To address this issue, an organization called Apollo Toronto was established at the University of Toronto in Toronto, Ontario. Apollo Toronto is a medical student-run international collaborative project between the Eureka Institute for Translational Medicine and the University of Toronto (one of Eureka Institute’s partner universities), and provides a general overview of TR to interested medical and graduate students. Through local and international initiatives, the various Apollo chapters (including Apollo Toronto) aim to establish a network of trainees equipped to address systemic issues that impede the translation of an ever-growing body of scientific literature into health solutions

Qualitative and quantitative measurement of the anterior and posterior meniscal root attachments of the New Zealand white rabbit

Background: The purpose of this study was to quantify the meniscal root anatomy of the New Zealand white rabbit to better understand this animal model for future in vitro and in vivo joint degeneration studies. Methods: Ten non-paired fresh frozen New Zealand white rabbit knee stifle joints were carefully disarticulated for this study. Measurements were made for all bony landmarks and ligamentous structure attachment sites on the tibial plateau. The following soft tissue structures were consistently identified in the rabbit stifle joint: the anterior root attachment of the lateral meniscus, the anterior root attachment of the medial meniscus, the anterior cruciate ligament, the posterior root attachment of the medial meniscus, the ligament of Wrisberg, the posterior cruciate ligament, and the posterior meniscotibial ligament. The following bony landmarks were consistently identified: the extensor digitorum longus groove, the medial tibial eminence, the center of the tibial tuberosity, and the lateral tibial eminence. Results: The center of the anterior cruciate ligament and the medial tibial eminence apex were found to be 3.4 ± 0.3 mm (2.9–3.6) and 6.1 ± 0.6 mm (5.1–7.0) respectively from the center of the medical anterior root attachment. The center of the anterior cruciate ligament and the lateral tibial eminence apex were found to be 2.1 ± 0.5 mm (1.2–2.7) and 7.0 ± 0.6 mm (6.4–8.2) respectively from the center of the lateral anterior root attachment. The center of the posterior cruciate ligament and the medial tibial eminence apex were found to be 2.0 ± 0.7 mm (0.5–2.6) and 1.8 ± 0.4 mm (1.2–2.4) respectively from the center of the medial posterior root attachment. Conclusions: This study augments our understanding of the comparative anatomy of the rabbit stifle joint. This information will be useful for future biomechanical, surgical, and in vitro studies utilizing the rabbit stifle as a model for human knee joint degenerative diseases

Anatomic Double-Bundle Posterior Cruciate Ligament Reconstruction

The posterior cruciate ligament (PCL) is known to be the main posterior stabilizer of the knee. Anatomic single-bundle PCL reconstruction, focusing on reconstruction of the larger anterolateral bundle, is the most commonly performed procedure. Because of the residual posterior and rotational tibial instability after the single-bundle procedure and the inability to restore the normal knee kinematics, an anatomic double-bundle PCL reconstruction has been proposed in an effort to re-create the native PCL footprint more closely and to restore normal knee kinematics. We detail our technique for an anatomic double-bundle PCL reconstruction using Achilles and anterior tibialis tendon allografts