Fetal Adipose Tissue Research Articles

Adipose tissue and fetal programming

Adipose tissue function changes with development. In the newborn, brown adipose tissue (BAT) is essential for ensuring effective adaptation to the extrauterine environment, and its growth during gestation is largely dependent on glucose supply from the mother to the fetus. The amount, location and type of adipose tissue deposited can also determine fetal glucose homeostasis. Adipose tissue first appears at around mid-gestation. Total adipose mass then increases through late gestation, when it comprises a mixture of white and brown adipocytes. BAT possesses a unique uncoupling protein, UCP1, which is responsible for the rapid generation of large amounts of heat at birth. Then, during postnatal life some, but not all, depots are replaced by white fat. This process can be utilised to investigate the physiological conversion of brown to white fat, and how it is re-programmed by nutritional changes in pre- and postnatal environments. A reduction in early BAT deposition may perpetuate through the life cycle, thereby suppressing energy expenditure and ultimately promoting obesity. Normal fat development profiles in the offspring are modified by changes in maternal diet at defined stages of pregnancy, ultimately leading to adverse long-term outcomes. For example, excess macrophage accumulation and the onset of insulin resistance occur in an adipose tissue depot-specific manner in offspring born to mothers fed a suboptimal diet from early to mid-gestation. In conclusion, the growth of the different fetal adipose tissue depots varies according to maternal diet and, if challenged in later life, this can contribute to insulin resistance and impaired glucose homeostasis.

Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep

The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n = 10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n = 10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81 mg arginine/kg body weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.

Evaluation of nano-biphasic calcium phosphate ceramics for bone tissue engineering applications: In vitro and preliminary in vivo studies

Reconstruction of critical sized bone injuries is a major problem that continues to inspire the design of new materials and grafts. Natural ceramics (hydroxyapatite (HA) coralline HA, or synthetic HA) and β-tricalcium phosphate (β-TCP) are being explored for use as scaffolds in bone tissue engineering, among several other materials. The present study evaluated the bone forming capacity of nanosize bioceramics synthesized in situ in poly-vinyl alcohol (PVA) with different ratios of HA and β-TCP; the Ca/P ratio was 1.62 for bioceramic P1, 1.60 for P2 and 1.58 for P3. Further osteogenesis in vitro with mesenchymal stem cells (MSC) acquired from different sources for osteogenesis in vitro and their bone healing properties in vivo were also evaluated. MSC isolated from human placenta, Wharton's jelly from umbilical cord, fetal bone marrow and adipose tissue, cultured in the presence of nanosize bioceramic particles, were monitored for osteogenic differentiation. Placental cells showed the best osteogenic potential of the different MSC studied on the basis of expression of osteogenic markers. Complete regeneration of the damaged region was observed in vivo when MSC derived from placenta were used with nanoceramic (Ca/P ratio 1.58) in the experimental defect created in the femur of Wistar rats. Even small variation in the Ca/P ratio can alter the outcome of tissue constructs.

Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots1

Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the perirenal depot of OB versus CON fetuses, and specific fatty acid concentrations were altered (P < 0.05) in subcutaneous and pericardial adipose tissue because of maternal obesity. In conclusion, maternal obesity was associated with increased fetal adiposity, increased fatty acid and glucose transporters, and increased expression of enzymes mediating fatty acid biosynthesis in adipose depots. These alterations, if maintained into the postnatal period, could predispose the offspring to later obesity and metabolic disease.

Cellular and molecular large‐scale features of fetal adipose tissue: Is bovine perirenal adipose tissue Brown1685

Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large-scale-molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post-conception (dpc) with the aim of identifying key cellular and molecular events in AT growth. The increase in AT weight from 110 to 260 dpc resulted from an increase in adipocyte volume and particularly adipocyte number that were concomitant with temporal changes in the abundance of 142 proteins revealed by proteomics. At 110 and 180 dpc, we identified proteins such as TCP1, FKBP4, or HSPD1 that may regulate adipocyte precursor proliferation by controlling cell-cycle progression and/or apoptosis or delaying PPARγ-induced differentiation. From 180 dpc, the up-regulation of PPARγ-induced proteins, lipogenic and lipolytic enzymes, and adipokine expression may underpin the differentiation and increase in adipocyte volume. Also from 180 dpc, we unexpectedly observed up-regulations in the β-subunit of ATP synthase, which is normally bypassed in brown AT, as well as in aldehyde dehydrogenases ALDH2 and ALDH9A1, which were predominantly expressed in mouse white AT. These results, together with the observed abundant unilocular adipocytes at 180 and 260 dpc, strongly suggest that fetal bovine perirenal AT has much more in common with white than with brown AT.

Foetal bovine intermuscular adipose tissue exhibits histological and metabolic features of brown and white adipocytes during the last third of pregnancy

This study reports the metabolic and morphological characteristics of bovine intermuscular adipose tissue (AT) throughout foetal growth. Our hypothesis was that the histological and molecular features of intermuscular AT would be different from those previously reported for foetal perirenal AT, based on its anatomical location near the muscle and the recent identification of two distinct adipocyte precursors in mouse AT depending on their locations. To address this question, intermuscular AT was sampled from Charolais and Blond d'Aquitaine foetuses at 180, 210 and 260 days post conception (dpc). The two bovine breeds were chosen because of the higher adiposity of Charolais than Blond d'Aquitaine cattle during the postnatal life. Regardless of the breed, adipocyte volume increased slightly (+38%, P < 0.01) with increasing foetal age. This was concomitant with a decrease (P < 0.05) in the activity of enzymes involved in de novo fatty acid (FA) synthesis (FA synthase and glucose-6-phosphate dehydrogenase) and FA esterification (glycerol-3-phosphate dehydrogenase) when expressed per million adipocytes, and with an increase (P ⩽ 0.01) in mRNA abundances for uncoupling protein 1, adiponectin and leptin (LEP) between 180 and 260 dpc. No difference was observed in the adipocyte volume between breeds, which was consistent with the lack of major between-breed differences in mRNA abundances or activities of enzymes involved in lipid metabolism. The mRNA abundance of lipoprotein lipase was maintained across ages, suggesting a storage of circulating FA rather than of FA synthesized de novo. Plasma LEP increased with foetal age, but only in the Charolais breed (+71%, P ⩽ 0.01), and was two- to threefold higher in Charolais than Blond d'Aquitaine foetuses. Regardless of the breed, bovine intermuscular AT contained predominantly unilocular adipocytes believed to be white adipocytes that were larger at 260 dpc than at 180 dpc. These data thus challenge current concepts of the largely brown nature of bovine foetal AT (based on histological and metabolic features of perirenal AT as previously reported a few days before or after birth).

Prenatal Effects of Different Intra-Uterine Milieus on Fetal Glucose Sensing Mechanisms during Gestation in Rats

The intra-uterine milieu programs the health of an individual throughout life. This effect has been called fetal origin of adult disease. The altered maternal metabolism is associated with a diabetogenic effect in the adult offspring. The pancreatic glucose-stimulated insulin secretion (GSIS) and peripheral response to insulin are central in glucose homeostasis in fetal circulation and the modulation of these processes during the fetal development may have a serious complications long-lasting. This study was aimed to delineate the prenatal (at gestational day 17) effects of different maternal health challenges on the fetal glucose sensing mechanisms including GLUT2, glucokinase, mitochondrial transcription factor A (mTFA), uncoupling protein 2 (UCP2), phospho-insulin receptor (Phosho-IR) and glucose transporter 4 (GLUT4). We used hyperglycemic, obese and malnourished beside normal female rats to establish pregnancy that was terminated at GD 17. The fetal pancreas, liver, muscle and adipose tissues were obtained for determination of the studied parameters. The results indicated up-regulation of GLUT2, glucokinase, mtTFA and UCP2 expression in fetal pancreas and liver of hyperglycemic mothers fetuses while maternal obesity mildly up-regulate expression of GLUT2, glucokinase and UCP2 in fetal pancreas, liver and adipose tissues, while malnutrition causes down-regulation of UCP2 in pancreas, it up-regulates GLUT2 and glucokinase in liver. In muscle and adipose tissues the level of phosho-IR was increased under maternal hyperglycemia and malnutrition while GLUT4 level increased under maternal diabetes only. We can conclude that the fetal adverse environments can prenatally affect the expression of genes that linked to the development of type 2 diabetes including genes controlling glucose sensing and metabolism.

In UteroProgramming of Later Adiposity: The Role of Fetal Growth Restriction

Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation.

Bir Çocukta Spermatik Kord Hibernoması

Hibernomas are rare benign neoplasms derived from the remnants of fetal brown adipose tissue, seen mainly in adults. Most of them are located in areas that normally include brown-fat remnants. Although these tumors are considered benign and malignant transformation has not been reported, they tend to grow into large sizes. If a hibernoma is detected during inguinoscrotal approaches, it should be excised totally because of the risk of growth. To date, recurrence has not been described following complete excision, which is therefore recommended as the treatment of choice. We would like to present an 11-month-old child with hibernoma of the spermatic cord which was surgically treated. One child presenting such a lesion has previously been reported in the literature.

Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep

Intrauterine growth restriction is a significant problem worldwide, resulting in increased rates of neonatal morbidity and mortality, as well as increased risks for metabolic and cardiovascular disease. The present study investigated the role of maternal undernutrition and L-arginine administration on fetal growth and development. Embryo transfer was utilized to generate genetically similar singleton pregnancies. On Day 35 of gestation, ewes were assigned to receive either 50 or 100% of their nutritional requirements. Ewes received i.v. injections of either saline or L-arginine three times daily from Day 100 to Day 125. Fetal growth was assessed at necropsy on Day 125. Maternal dietary manipulation altered circulating concentrations of leptin, progesterone, and amino acids in maternal plasma. Fetal weight was reduced in nutrient-restricted ewes on Day 125 compared with 100% fed ewes. Compared with saline-treated underfed ewes, maternal L-arginine administration did not affect fetal weight but increased weight of the fetal pancreas by 32% and fetal peri-renal brown adipose tissue mass by 48%. These results indicate that L-arginine administration enhanced fetal pancreatic and brown adipose tissue development. The postnatal effects of increased pancreatic and brown adipose tissue growth warrant further study.

Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue

Background Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT). Objective & design To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100 g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants. Results From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298 mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226 mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2 mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55 g%, MUFA decreased from 44 to 41 g%, and PUFA from 10.3 to 4.26 g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193 mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500 g LGA infants were 184 and 402 mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher. Conclusion FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature.

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: The influence of extracellular matrix on intramuscular and extramuscular adipogenesis1

The extracellular matrix (ECM) and specific ECM components can have a major influence on cell growth, development, and phenotype. The influence of the ECM and ECM components on adipogenesis in vivo and in vitro will be reviewed in this paper. Engelbreth-Holm-Swarm substratum and laminin per se markedly increased attachment, spreading, and hypertrophy of preadipocytes in serum-free primary cultures of porcine adipose tissue stromal-vascular cells. Furthermore, primary cultures of stromal-vascular cells showed that preadipocytes express ECM components after preadipocyte recruitment. Staining for plant lectins, type IV collagen, and laminin in fetal pig adipose tissue demonstrates that adipocyte reactivity for laminin was strong throughout fetal development and was similar for developing adipocytes and vasculature. However, lectin binding and type IV collagen reactivity of blood vessels preceded that for adipocytes. Therefore, these studies indicated that the ECM and in particular laminin may play a critical role in morphological aspects of preadipocyte development. Specific inhibitors and modulators of collagen synthesis have been used to evaluate the role of collagens in the differentiation of bovine intramuscular preadipocytes (BIP) and other preadipocyte cell lines. Triglyceride accretion of BIP cells was inhibited by a general inhibitor of collagen biosynthesis, whereas specific inhibitors or modulators of type IV collagen inhibited 3T3-L1 cell differentiation. Further study revealed that compared with collagens types I to IV, type V and VI collagens have an important and active role in BIP adipogenesis. The growth of intramuscular bovine adipose tissue may be dependent on collagen newly synthesized and organized by the adipocytes per se. The role of extracellular or ECM proteolysis in regulating adipogenesis also will be reviewed in this paper. Many members of the matrix metalloproteinase (MMP) family are expressed by adipocytes, and specific inhibition of MMP-9 greatly reduces adipogenesis in vitro. Possibly, MMP and other proteases regulate turnover of key adipocyte ECM proteins that are involved in the regulation of preadipocyte proliferation and differentiation.

RUMINANT NUTRITION SYMPOSIUM: OPTIMIZING PERFORMANCE OF THE OFFSPRING: Nourishing and managing the dam and postnatal calf for optimal lactation, reproduction, and immunity1,2

For several mammalian species, it has been shown that fetal and early postnatal nutrition has a role in long-term lipid and glucose metabolism of the offspring, and it thus also may have consequences on milk yield in the dairy cow. For instance, high-energy diets during the last weeks of pregnancy may result in increased glycemia, which in turn, may alter fetal adipose tissue development. However, most research efforts on management and nutrition of dry cows have focused on minimizing metabolic disorders of the postpartum cow without devoting much attention to potential consequences for the offspring. Similarly, nutritional needs for proper placental development and early fetal growth have received little attention, despite the fact that alterations in placental and fetal development may alter expression of genes participating in homeorhesis of the offspring. Therefore, nutrition of the pregnant cow, both while lactating and dry, should also consider aspects of placental and fetal development that may affect health and performance of the progeny. Similarly, newborn calves and young heifers are fed to ensure a particular growth target without compromising mammary development, although data linking postnatal growth targets with future milk yield are scarce. However, milk yield not only depends on mammary development, but also on nutrient partitioning, which is regulated by the endocrine milieu. There are some periods of time during development where nutrition may have long-lasting effects on metabolic function and milk production. For instance, the first months of postnatal life seem to be critical because recent data from both retrospective and controlled studies indicate that increased growth rate or plane of nutrition during this phase is positively associated with future milk production. Postnatal growth rate depends on nutrition (a necessary but not sufficient condition) and management (i.e., grouping strategies and housing systems), and thus optimal rearing programs should be designed considering long-term consequences on milk yield.

Heifer nutrient intake during early- and mid-gestation programs adult offspring adiposity and mRNA expression of growth-related genes in adipose depots

Changes in maternal nutrient intake during gestation alter IGF receptor abundance and leptin (LEP) mRNA expression in fetal adipose tissue. It is not known whether such changes persist into adult life and whether they are associated with an effect on phenotype. We investigated the effect of high (240%) and low (70%) levels of recommended daily crude protein intake for beef heifers during the first and second trimesters of gestation on singleton progeny (n=68): subcutaneous (SC) adipose tissue depth at rump (P8) and rib (RF) sites from 65 until 657 days of age; plasma leptin concentrations from birth until 657 days and expression of IGF1 and IGF2, their receptors (IGF1R and IGF2R) and LEP mRNA in perirenal (PR), omental (OM) and SC adipose tissue at 680 days of age. High-protein diets during the first trimester increased LEP and IGF1 mRNA in PR of males and females, respectively, compared with low-protein diets, and decreased IGF1R mRNA in SC of all progeny but increased RF depth of males between 552 and 657 days. High-protein diets compared with low-protein diets during the second trimester increased IGF1R mRNA in PR and OM of all progeny; LEP mRNA in PR of males; and IGF2 and IGF2R mRNA in OM of all progeny. Conversely, LEP mRNA in OM and IGF2 mRNA in PR of all progeny were decreased following exposure to high- compared with low-protein diets during the second trimester. Heifer diet during gestation has permanent sex- and depot-specific effects on the expression of adipogenic and adipocytokine genes and offspring adiposity.

Cells Behaviour in Presence of Nano-Scaffolds

Nanomaterials are being made for use in various fields in biology from sensors to clutches. Nanomaterials may be perceived, in bizarre ways by the cells. Starting from the membrane to the nucleus, each component of the cell could have a new response. Mesenchymal Stem Cells (MSC) isolated from human placenta, Wharton's jelly, cord blood, fetal bone marrow and adipose tissue, cultured in the presence of biomaterials were monitored for differentiation in to the osteogenic phenotype. On the basis of osteogenic marker expression analysis, placental cells exhibited the best osteogenic potential among the different MSC. There is some cell death initially but the cells that remain viable show uptake of nanoparticles. The viable cells both divide and show differentiation into osteogenic cell type. The placental MSC in conjunction with the biomaterials were implanted in the injured femur of Wistar rats showed complete regeneration of the damaged region.

β2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction

Placental insufficiency-induced intrauterine growth restriction (IUGR) fetuses have chronic hypoxaemia and elevated plasma catecholamine concentrations. In this study, we determined whether adrenergic responsiveness becomes desensitized in the perirenal adipose tissue of IUGR fetuses and lambs by measuring adrenergic receptor (AR) mRNA and protein levels. We also tested the ability of adrenaline to mobilize non-esterified fatty acids (NEFAs) in young lambs. Perirenal adipose tissue was collected from IUGR and control fetuses at 133 days of gestational age (dGA) and lambs at 18 days of age (dA). β(2)-AR mRNA concentrations were 59% and 74% lower (P < 0.05) in IUGR fetuses and lambs compared to controls, respectively, which also resulted in lower protein levels (P < 0.05). No treatment differences were detected for α(1A)-, α(1B)-, α(1D)-, α(2A)-, α(2B)-, α(2C)-, β(1)- and β(3)-AR expression. mRNA concentrations were also determined for hormone sensitive lipase (HSL), perilipin (lipid droplet-associated protein), and two adipokines, leptin and adiponectin. Adiponectin and HSL were not different between treatments at either age. Compared to controls, perilipin and leptin mRNA concentrations were lower (P < 0.05) in IUGR fetuses but not in lambs. Because of the β(2)-AR results, we challenged a second cohort of lambs with exogenous adrenaline at 21 dA. The ability of adrenaline to mobilize NEFA was 55 ± 15% lower (P < 0.05) in IUGRs than controls. Collectively, our findings indicate that elevated catecholamine exposure in utero causes desensitization of adipose tissue by down-regulation of β(2)-AR, and this persists in lambs. This impairment in adrenergic stimulated lipolysis might partially explain early onset obesity in IUGR offspring.

Cell death‐inducing DFF45‐like effector, a lipid droplet‐associated protein, might be involved in the differentiation of human adipocytes

Cell death-inducing DFF45-like effector (CIDE) family proteins, including cell death-inducing DFF45-like effector A (CIDEA), cell death-inducing DFF45-like effector B (CIDEB) and cell death-inducing DFF45-like effector C (CIDEC) [fat-specific protein of 27 kDa in rodent (FSP27) in rodents], were originally identified by their sequence homology to the N-terminal region of DNA fragmentation factor DFF40/45. Recent reports have revealed that CIDE family proteins play important roles in lipid metabolism. Several studies involving knockdown mice revealed that FSP27 is a lipid droplet-targeting protein that can promote the formation of lipid droplets. However, the detailed roles of human CIDEC in the differentiation of human adipocytes remain unknown. In the present study, we found that the expression of CIDEC increased during the differentiation of fetal adipose tissues, but decreased during the de-differentiation of adipocytic tumors, suggesting that the expression of CIDEC should be positively correlated with the differentiation of adipocytes. Furthermore, we verified that human CIDEC was localized on the surface of lipid droplets. Using human primary pre-adipocytes, we confirmed that the expression of CIDEC was elevated during the differentiation of pre-adipocytes, and knockdown of CIDEC in human primary pre-adipocytes resulted in differentiation defects. These data demonstrate that CIDEC is essential for the differentiation of adipose tissue. Together with regulating adipocyte lipid metabolism, CIDEC should be a potential target for regulating adipocyte differentiation and reducing fat cell mass.

Distribution of PCB 118 and PCB 153 and hydroxylated PCB metabolites (OH-CBs) in maternal, fetal and lamb tissues of sheep exposed during gestation and lactation

The main objective of the present study was to gain knowledge about the disposition of the PCB congeners 118 and 153 in a sheep model where ewes were given oral doses of PCB in two consecutive gestations. The study aimed to investigate how maternal exposure with PCBs affected tissue concentrations in lambs and fetuses and to carry out time trend studies in ewes between gestations, as well as to increase the knowledge on metabolic processes by studying OH-metabolites. The results showed that the fetuses accumulated PCBs in levels and composition comparable to the ewes. The mean fetus/mother ratios of adipose tissue levels ranged from 0.71 to 0.82 for both PCB 118 and PCB 153 in the two exposure groups. Furthermore, the fetal brain/fat ratios ranged from 0.15 to 0.20 for both congeners. Body burden calculations (BB) showed that 16% and 43% of the total PCB 118 and PCB 153, respectively, still remained in ewes, lambs and fetuses after exposure during two gestations. The different accumulation of the two congeners is assumed to be a result of differences in metabolism. The present study demonstrate that high levels of PCB 118 and PCB 153 cross the placenta and accumulate in the fetal adipose tissue and brain thus exposing the fetus during vulnerable periods of extensive development.

Fatty Acid Supply to the Human Fetus

Deposition of fat in the fetus increases exponentially with gestational age, reaching its maximal rate-around 7 g/day or 90% of energy deposition-at term. In late pregnancy, many women consuming contemporary Western diets may not be able to meet the fetal demand for n-3 long chain polyunsaturated fatty acids (LCPUFAs) from the diet alone. Numerous mechanisms have evolved to protect human offspring from extreme variation or deficiency in the maternal diet during pregnancy. Maternal adipose tissue is an important source of LCPUFA. Temporal changes in placental function are synchronized with maternal metabolic and physiological changes to ensure a continuous supply of n-3 and n-6 LCPUFA-enriched fat to the fetus. LCPUFA storage in fetal adipose tissue provides an important source of LCPUFA during the critical first months of postnatal life. An appreciation of these adaptations is important in any nutritional strategy designed to improve the availability of fatty acids to the fetus.

Nutrition during mid to late gestation affects growth, adipose tissue deposition, and tenderness in cross-bred beef steers

The objective of this study was to examine whether the plane of nutrition of cows at a critical time for fetal skeletal muscle and adipose tissue development would affect meat quality and carcass composition of offspring. To alter maternal nutrition, beef cows were placed on improved pasture (IP) or native range (NR) pasture from 120 to 150 through 180 to 210days of gestation. Esophageal extrusa samples collected from cows grazing IP varied from 11.1% crude protein of organic matter early in the test period to 6.0% crude protein of organic matter at the end of the grazing period; whereas, extrusa samples of cows grazing NR ranged from 6.5% crude protein of organic matter during early grazing to 5.4% crude protein of organic matter at the end of the grazing period. Steers were slaughtered and carcass characteristics were collected. Warner-Bratzler shear force was performed on longissumus steaks, western blotting was used to measure proteolysis, and myosin isoform typing was performed. Improved pasture steers had heavier live and hot carcass weights. Tenderness was greater in IP compared to NR steers. No difference in calpastatin content and troponin-T degradation was observed between treatments. The 12th rib fat thickness was greater for IP than for NR steers. Subcutaneous adipose tissue of IP steers tended to have a greater number of cells per field of view than NR steers. Data show improving nutritional status of cows during mid to late gestation affects tenderness, adipose tissue deposition and growth in steers.