Gene pathway development in human epicardial adipose tissue during early life

Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life

Molecular characterization of adipose tissue in the African elephant (Loxodonta africana)

Adipose tissue (AT) is a dynamic and flexible organ with regulatory roles in physiological functions including metabolism, reproduction and inflammation; secreted adipokines, including leptin, and fatty acids facilitate many of these roles. The African elephant (Loxodonta africana) is experiencing serious challenges to optimal reproduction in captivity. The physiological and molecular basis of this impaired fertility remains unknown. AT production of leptin is a crucial molecular link between nutritional status, adiposity and fertility in many species. We propose that leptin has a similar function in the African elephant. African elephant visceral and subcutaneous adipose tissue (AT) was obtained from both sexes and a range of ages including females with known pregnancy status. RNA was extracted and histological sections created and analyzed by microarray, PCR and immunohistochemistry respectively. Gas-chromatography was used to determine the fatty acid composition of AT. Microarray expression profiling was used to compare gene expression profiles of AT from pre-pubertal versus reproductively competent adult African elephants. This study demonstrates, for the first time, leptin mRNA and protein expression in African elephant AT. The derived protein sequence of the elephant leptin protein was exploited to determine its relationship within the class I helical cytokine superfamily, which indicates that elephant leptin is most closely related to the leptin orthologs of Oryctolagus cuniculus (European rabbit), Lepus oiostolus (woolly hare), and members of the Ochotonidae (Pika). Immunohistological analysis identified considerable leptin staining within the cytoplasm of adipocytes. Significant differences in fatty acid profiles between pregnant and non-pregnant animals were revealed, most notably a reduction in both linoleic and α linoleic acid in pregnant animals. This report forms the basis for future studies to address the effect of nutrient composition and body condition on reproduction in captive and wild elephants

Impact of maternal dietary fat supplementation during gestation upon skeletal muscle in neonnatal pigs

Background Maternal diet during pregnancy can modulate skeletal muscle development of the offspring. Previous studies in pigs have indicated that a fat supplemented diet during pregnancy can improve piglet outcome, however, this is in contrast to human studies suggesting adverse effects of saturated fats during pregnancy. This study aimed to investigate the impact of a fat supplemented (palm oil) “high fat” diet on skeletal muscle development in a porcine model. Histological and metabolic features of the biceps femoris muscle obtained from 7-day-old piglets born to sows assigned to either a commercial (C, n = 7) or to an isocaloric fat supplementation diet (“high fat” HF, n = 7) during pregnancy were assessed. Results Offspring exposed to a maternal HF diet demonstrated enhanced muscular development, reflected by an increase in fractional growth rate, rise in myofibre cross-sectional area, increased storage of glycogen and reduction in lipid staining of myofibres. Although both groups had similar intramuscular protein and triglyceride concentrations, the offspring born to HF mothers had a higher proportion of arachidonic acid (C20:4n6) and a reduction in a-linolenic acid (C18:3n3) compared to C group offspring. The HF group muscle also exhibited a higher ratio of C20:3n6 to C20:4n6 and total n-6 to n-3 in conjunction with up-regulation of genes associated with free fatty acid uptake and biogenesis. Conclusion In conclusion, a HF gestational diet accelerates the maturation of offspring biceps femoris muscle, reflected in increased glycolytic metabolism and fibre cross sectional area, differences accompanied with a potential resetting of myofibre nutrient uptake

Reduced neonatal mortality in Meishan piglets: a role for hepatic fatty acids?

The Meishan pig breed exhibits increased prolificacy and reduced neonatal mortality compared to commercial breeds, such as the Large White, prompting breeders to introduce the Meishan genotype into commercial herds. Commercial piglets are highly susceptible to hypoglycemia, hypothermia, and death, potentially due to limited lipid stores and/or delayed hepatic metabolic ability. We therefore hypothesized that variation in hepatic development and lipid metabolism could contribute to the differences in neonatal mortality between breeds. Liver samples were obtained from piglets of each breed on days 0, 7, and 21 of postnatal age and subjected to molecular and biochemical analysis. At birth, both breeds exhibited similar hepatic glycogen contents, despite Meishan piglets having significantly lower body weight. The livers from newborn Meishan piglets exhibited increased C18∶1n9C and C20∶1n9 but lower C18∶0, C20∶4n6, and C22∶6n3 fatty acid content. Furthermore, by using an unsupervised machine learning approach, we detected an interaction between C18∶1n9C and glycogen content in newborn Meishan piglets. Bioinformatic analysis could identify unique age-based clusters from the lipid profiles in Meishan piglets that were not apparent in the commercial offspring. Examination of the fatty acid signature during the neonatal period provides novel insights into the body composition of Meishan piglets that may facilitate liver responses that prevent hypoglycaemia and reduce offspring mortality

Heat maps and principal component analysis of fatty acid profiles.

<p>Heat maps and dendrograms visualizing the hierarchical clustering results (average linkage, Euclidean distance metric) of Meishan (A) and commercial piglets (B). Rows correspond to animals and the corresponding age group is indicated by coloured circles. The fatty acid mole percentiles were transformed to a z-score and indicated by a colour code, with red representing low percentiles and green high percentiles. Principal component analysis (PCA) plots of all Meishan (C) and all commercial piglets (D).</p

Body and liver weight with age and breed.

<p>Influence of breed on early growth in Meishan (open bars) and commercial (closed bars) piglets during the first 21 days postnatal life. (A) Changes in body weight, (B) Changes in liver weight and (C) Relative liver weight. A; p<0.05: statistical difference between the Meishan breed age groups, B; p<0.05: Statistical difference between the commercial age groups, C; p<0.05: Statistical difference between the 0 and 7 day old in comparison to 21 days old commercial breed group and *; p<0.05: Statistical difference between the same postnatal age groups. Bar graphs illustrate means ± SEM.</p

Fatty acid profiles.

<p>Differences of the major fatty acids in the livers of Meishan (open bars) and commercial (grey bars) piglets over the first 21 days of postnatal life. (A) stearic acid, (B) heptadecanoic acid, (C) oleic acid, (D) eicosenoic acid (E) arachidonic acid, (F) docosahexaenoic acid. A; p<0.05: statistical difference between the 0 and the other age groups within Meishan breed group. B; p<0.05: Statistical difference between the same postnatal age groups. Bar graphs illustrate means ± SEM.</p

Liver composition between age and breed.

<p>The effect of breed and postnatal age in liver composition between Meishan (open bars) and commercial (closed bars) piglets: (A) Triglyceride content and (B) glycogen content. *; p<0.05: statistical difference between the same postnatal age groups. Bar graphs illustrate means ± SEM.</p

mRNA expression of hepatic metabolic genes between breed and age.

<p>mRNA abundance of <i>FAS</i>, <i>SCD-</i>1, <i>ELOVL</i>-6 and <i>CoA</i> in the liver of newborn Meishan (open bars) or commercial (closed bars) piglets as determined by real time PCR. Bar graph illustrates means ± SEM with statistically significant differences between groups represented by *p<0.05.</p