Gestational changes in concentrations of selenium and zinc in the porcine fetus and the effects of maternal intake of selenium

The effect of maternal dietary selenium (Se) and gestation on the concentrations of Se and zinc (Zn) in the porcine fetus were determined. Mature gilts were randomly assigned to treatments of either adequate (0.39 ppm Se) or low (0.05 ppm Se) dietary Se. Gilts were bred and fetuses were collected throughout gestation. Concentrations of Se in maternal whole blood and liver decreased during gestation in sows fed the low-Se diet compared to sows fed the Se-supplemented diet. Maternal intake of Se did not affect the concentration of Se in the whole fetus; however, the concentration of Se in fetal liver was decreased in fetuses of sows fed the low-Se diet. Although fetal liver Se decreased in both treatments as gestation progressed, the decrease was greater in liver of fetuses from sows fed the low-Se diet. Dietary Se did not affect concentrations of Zn in maternal whole blood or liver or in the whole fetus and fetal liver. The concentration of Se in fetal liver was lower but the concentration of Zn was greater than in maternal liver when sows were fed the adequate Se diet. These results indicate that maternal intake of Se affects fetal liver Se and newborn piglets have lower liver Se concentrations compared to their dams, regardless of the Se intake of sows during gestation. Thus, the piglet is more susceptible Se deficiency than the sow.     

Delayed muscle development in small pig fetuses around birth cannot be rectified by maternal early feed restriction and subsequent overfeeding during gestation

Intrauterine variations in nutrient allowance can alter body composition and tissue features of the porcine offspring around birth. This study aimed to determine the effects of fetal weight variations between littermates and of maternal dietary regimen during gestation on fetal muscle traits just before birth. Fourteen pregnant gilts were reared under a conventional (control, CTL; n=7) or an experimental (treatment, TRT; n=7) dietary regimen during gestation. The dietary treatment provided 70% of the protein and digestible energy contents of the CTL diet during the first 70 days of gestation and then, 115% of the protein and digestible energy contents up to farrowing. At 110 days of gestation, sows were sacrificed and one fetus having a low (824±140 g) and one having a normal (1218±192 g) BW per litter were sampled. Irrespective of maternal dietary regimen, the longissimus muscle of the small fetuses exhibited higher expression levels of DLK1/Pref1 and NCAM1/CD56, two genes known to be downregulated during normal skeletal muscle development. Expression levels of the embryonic isoform of the myosin heavy chain (MyHC), both at the mRNA and at the protein levels, were also higher in small fetuses. In addition, the ratios of perinatal to embryonic and of adult fast to developmental MyHC isoforms were generally lower in light fetuses compared with their medium-weight littermates. These modifications suggest a delayed myofiber development in spontaneous growth-retarded fetuses. Finally, GLUT1 was expressed to a lesser extent in the muscle of small v. normal fetuses, suggesting decreased ability for glucose uptake in muscle. Initial feed restriction and subsequent overfeeding of sows during gestation led to a lower expression of the myogenic factor MYOD1, a prerequisite for myogenic initiation in skeletal muscle. This maternal strategy was also associated with a lower expression level of insulin-like growth factor 1 receptor (IGFR) but an upregulation of IGF2. This suggests an altered susceptibility of muscle cells to IGFs’ signal in fetuses from treated sows. Altogether, intrauterine growth restriction impaired fetal muscle development, and restricted feeding followed by overfeeding of gestating sows did not allow small fetuses to recover normal contractile and metabolic characteristics.     

Histochemistry of connective tissue cells in subcutaneous adipose tissue of normal and decapitated pig fetuses

Connective tissue cells that are histochemically and morphologically distinct from 'fibroblasts' are localized around developing hair follicles in the pig and rat. Immature adipose tissue is limited to small areas immediately around fully descended hair follicles in the rat hypodermis. In the present study, connective tissue around large nerves and blood vessels in fetal pig subcutaneous tissue was examined for the presence of enzymes typical of adipocytes. Samples from decapitated pig fetuses were studied so that the effects of an altered hormonal profile could be examined. Samples of dorsal subcutaneous adipose tissue were obtained from fetuses at 65, 70, 85, 90, 110, and 112 days of gestation. Fetuses were decapitated in utero at 45 days of gestation, and adipose tissue samples were obtained from these fetuses at 110 days of gestation. A close spatial relationship was observed between the growth of large blood vessels and nerves and fat cell cluster development in the older (greater than 70 days) fetuses. Connective tissue cells that were contiguous with fat cell clusters were histochemically identical to adipocytes. The lipid histochemistry of the reactive connective tissue cells (histochemically identical to adipocytes) was variable in young fetuses. In all 110-and 112-day-old fetuses, the reactive cells contained lipid, whereas the reactive cells in decapitated fetuses were devoid of lipid. The reactive connective tissue cells were not associated with capillaries and did not contain basement membranes. The histochemistry of these cells suggests that they respond to a particular hormonal or metabolic profile as do adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of maternal nutrition on expression of genes responsible for adipogenesis and myogenesis in the bovine fetus

The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression. Samples from the LM and semitendinosus (ST) were evaluated for muscle fiber diameter, area and number. The right hind limb was dissected and analyzed to determine compositional analysis. Fetal growth and muscle histology characteristics of the LM and ST were similar among treatments. Preadipocyte factor-1 expression was up-regulated in fetal LM (P<0.05) of HIGH fetuses as compared with INT, whereas LOW fetuses showed increased CCAAT/enhancer-binding protein-β (C/EBP-β) expression in LM as compared with INT (P<0.05). Peroxisome proliferator-activated receptor γand C/EBP-α did not differ as a result of dietary treatment in LM or subcutaneous fat samples. There was a tendency for increased expression of fatty acid synthase in LM of LOW fetuses as compared with INT (P<0.10). Myogenin was more highly expressed (P<0.05) in LM of the LOW fetuses, whereas μ-calpain expression was increased in the HIGH treatment compared with INT. A tendency for increased expression of IGF-II was observed for both LOW and HIGH fetuses compared with INT (P<0.10). Expression of stearoyl-CoA desaturase, myoblast determination protein 1, myogenic factor 5, myogenic regulatory factor-4, m-calpain, calpastatin, IGF-I and myostatin was similar between treatments. Collectively, these results suggest that fetal growth characteristics are not affected by the level of maternal nutritional manipulation imposed in this study during mid-gestation. However, differences in expression of fetal genes regulating adipose and muscle tissue growth and development could lead to differences in postnatal composition and warrants further investigation.     

Effect of supplementation of the maternal diet with fish oil or linseed oil on fatty-acid composition and expression of Δ5- and Δ6-desaturase in tissues of female piglets

The present study investigated whether enrichment of the pig maternal diet with n-3 polyunsaturated fatty acids (PUFA) affects the fatty-acid composition of female piglets via enhancing of expression of the lipogenic enzymes Δ5-desaturase (Δ5d) and Δ6-desaturase (Δ6d). The sows (50% Landrace × 50% Large White) were fed a control diet or one of the experimental diets starting at day 45 in gestation. The experimental diets were supplemented either with linseed oil or fish oil, whereas the control diet contained palm oil. Expression of Δ5d and Δ6d, and fatty-acid composition was determined by Western blotting and gas-liquid chromatography, respectively, in muscle, subcutaneous adipose tissue and liver. The highest Δ5d protein expression was observed in the piglets’ muscle, followed by subcutaneous adipose tissue, with the lowest level in the liver. Expression of Δ6d in the piglets’ tissues followed an opposite pattern, and was highest in the liver, followed by subcutaneous adipose tissue, with the lowest level in muscle. Supplementation of the maternal diet with fish oil or linseed oil increased the level of n-3 PUFA of the piglets in a tissue-specific manner. The response of Δ6d and Δ5d protein expression in female piglets, with average birth weight 2.4 kg, to the dietary manipulation was also tissue-specific. It is suggested that the increase in n-3 PUFA content in the progeny was related, at least partially, to the activation of Δ6d and Δ5d expression.     

Fat supplementation to the gestation diet of older sows and its effect on maternal and fetal fat metabolism

Sows that had had 3 previous litters were fed either a diet with no added fat (low fat) which was rich in linoleic acid (56.7% 18:2n-6), or a high fat diet containing lard, high in total saturates (28.9%) and oleic acid (37.8% 18:1n-9) during gestation. Backfat build-up in the sows on the high fat diet was accelerated compared to the low fat group. On day 110 of gestation, fetuses were removed. The fat content of the diet had no significant effect on sow weight gain during gestation, and the number or body weight of fetuses. Activities of sow liver and adipose and fetal liver malic enzyme, glucose-6-phosphate dehydrogenase (G-6-P) and acetyl-CoA-carboxylase (ACoABx) were measured. Only fetal liver ACoABx and sow adipose G-6-P were significantly affected by the sow's diet.     

Adrenergic innervation of fetal pig adipose tissue. Histochemical and ultrastructural studies

Histochemistry and electron microscopy were used to study the adrenergic innervation of subcutaneous adipose tissue in fetal pigs. Adrenergic innervation was present around arteries, arterioles, and adipocyte-associated capillaries. Nerve fibers were infrequently observed around veins, venules, and adipocytes. Ultrastructural features of nerves included mitochondria, clear synaptic vesicles, and a small number of vesicles with a core of electron-dense material. Innervation of adipose tissue was similar in 70-, 90-, and 110-day-old fetuses. Examination of fetuses decapitated at 45 days of gestation and removed at 110 days showed that adrenergic innervation was absent in adipose tissue of decapitated fetuses. Adrenergic innervation was also absent in adipose tissue from fetuses hypophysectomized at 72-73 days of gestation and examined at 110 days. These data indicate that fetal porcine adipose tissue may be under neural control by day 70 of gestation. Furthermore, an intact pituitary is necessary for the development of adrenergic innervation in fetal adipose tissue.     

Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep

Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P < 0.0001), mean gestational arterial Po(2) (P < 0.0001), plasma glucose (P < 0.01), and insulin concentrations (P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 +/- 0.063; control, 0.741 +/- 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 +/- 0.009; control, 0.115 +/- 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity.     

Growth and development of offspring following supplementation of sow diets with oil during early to mid gestation

The role of dietary fat during early pregnancy in sows has not yet been fully established. The aim of the study was to determine the consequences of altering the fatty acid profile of sow diets during the first half of gestation; oils of different fatty acid composition were chosen as energy supplements to provide diets with different fatty acid profiles. A group of 48 multiparous sows were used to evaluate the effects of supplemental feeding during the first 60 days of gestation (term ≈ 115 days). Sows were allocated (eight per treatment) to either 3 kg/day of commercial sow pellets (control; C) or an experimental diet consisting of 3 kg/day of commercial sow pellets supplemented with 10% extra energy in the form of excess pellets (E), palm oil (P), olive oil (O), sunflower oil (S) or fish oil (F). Differential effects were observed with respect to the fatty acid profile of the diet during the first half of gestation. P sows gave birth to the largest litters. Both P and O supplementation of the maternal diet resulted in heavier piglets at birth, after correction for differences in litter size. P piglets possessed the most fat at birth and remained fatter throughout the pre-weaning period; in contrast, the offspring of O sows contained the least fat throughout life (0 to 140 days of age). The offspring of F sows exhibited improved growth performance during the neonatal period. In conclusion, altering the fatty acid profile of sow diets during the first half of gestation has long-term consequences for the growth and development of their offspring.     

Lipid composition of lactational diets influences the fatty acid profile of the progeny before and after suckling

The purpose of the present study was to compare the influence of adding no or 8% fat of varying sources (coconut oil, fish oil, rapeseed oil and sunflower oil) to diets for sows 1 week prior to farrowing and during lactation on the composition of fatty acids in plasma and tissues of the progeny while sucking and 3 weeks after weaning from the sow. A control diet without supplemental fat and four diets supplemented with 8% of coconut oil, rapeseed oil, fish oil or sunflower oil were provided to lactating sows (n = 15), and during the post-weaning period the same weaner diet was provided to all piglets (n = 15 litters), which were housed litterwise. The dietary ratio of n-6:n-3 fatty acids of the maternal diets largely influenced the progeny, as the ratio varying from 1.2 (fish oil) to 12.2 (sunflower oil) in the sow milk was reflected in plasma and adipose tissues of the sucking progeny. The liver showed similar variations according to dietary treatments, but a lower n-6:n-3 fatty acids ratio. From day 4 to later on during the suckling period, the concentration of C14:0, C16:0 and C18:1 in the liver of the piglets decreased, irrespective of the dietary treatments of sows. In plasma and liver, the total concentration of saturated fatty acids (SAFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) did not differ markedly in piglets sucking sows fed different dietary fatty acids, whereas the adipose tissue of piglets sucking sows fed sunflower oil and coconut oil showed the highest proportion of PUFA and SAFA, respectively. Weaning lowered the concentration of lipid-soluble extracts in plasma and the concentration of fatty acids in the liver of the piglets. Within the post-weaning period, dietary treatments of sows, rather than age of piglets, influenced the fatty acid composition of plasma and adipose tissue of the piglets, whereas the hepatic fatty acid profile was more affected by the age of the piglets during the post-weaning period. This study shows that the fatty acid profile of plasma and tissues of the progeny is highly dependent on the maternal dietary composition, and that the dietary impact persists for up to 3 weeks after the suckling period.     

The Expression of Peroxisome Proliferator‐Activated Receptor γ in Pig Fetal Tissue and Primary Stromal‐Vascular Cultures

Objective: This study was designed to determine when peroxisome proliferator‐activated receptor γ (PPARγ) is expressed in developing fetal adipose tissue and stromal‐vascular adipose precursor cells derived from adipose tissue. In addition we examined developing tissue for CCAAT/enhancer‐binding protein β (C/EBPβ) expression to see if it was correlated with PPARγ expression. Pituitary function and hormones involved with differentiation (dexamethasone and retinoic acid) were also tested for their effects on PPARγ expression to determine if hormones known to affect differentiation also effect PPARγ expression in vivo and in cell culture. Research Methods and Procedures: Developing subcutaneous adipose tissues from the dorsal region of the fetal pig were collected at different gestation times and assayed using Western blot analysis to determine levels of PPARγ and C/EBPβ. Hypophysectomy was performed on 75‐day pig fetuses and tissue samples were then taken at 105 days for Western blot analysis. Adipose tissue was also taken from postnatal pigs to isolate stromal‐vascular (S‐V) cells. These adipose precursor cells were grown in culture and samples were taken for Western blot analysis to determine expression levels of PPARγ. Results: Our results indicate that PPARγ is expressed as early as 50 days of fetal development in adipose tissue and continues through 105 days. Expression of PPARγ was found to be significantly enhanced in adipose tissue from hypophysectomized fetuses at 105 days of fetal development (p < 0.05). C/EBPβ was not found in 50‐ or 75‐day fetal tissues and was found only at low levels in 105‐day tissues. C/EBPβ was not found in hypophysectomized (hypoxed) 105‐day tissue where PPARγ was elevated. S‐V cells freshly isolated from adipose tissue of 5‐ to 7‐day postnatal pigs showed the expression of PPARγ1. When S‐V cells were cultured, both PPARγ1 and 2 were expressed after the first day and continued as cells differentiated. High concentrations of retinoic acid decreased PPARγ expression in early S‐V cultures (p < 0.05). Discussion: Our data indicate that PPARγ is expressed in fetal adipose tissue very early before distinct fat cells are observed and can be expressed without the expression of C/EBPβ. The increase in PPARγ expression after hypophysectomy may explain the increase in fat cell size under these conditions. Adipose precursor cells (S‐V cells) from 5‐ to 7‐day postnatal pigs also express PPARγ in the tissue before being induced to differentiate in culture. Thus S‐V cells from newborn pig adipose tissue are probably more advanced in development than the 3T3‐L1 cell model. S‐V cells may be in a state where PPARγ and C/EBPα are expressed but new signals or vascularization are needed before cells are fully committed and lipid filling begins.     

Effect of dietary fat or starch supply during gestation and/or lactation on the performance of sows, piglets' survival and on the performance of progeny after weaning

Two trials were carried out to compare the effects of fat or starch inclusion in sow's diet on sow and litter performance. In each trial, sows were assigned to one of two treatments. In trial 1, the sows were fed diets containing either soybean oil (5%, treatment GL5) or cornstarch (11.3%, GL0) from day 35 of gestation to weaning. Daily net energy and nutrient allowance were equalised during gestation. In trial 2, the same treatments were applied only after farrowing (treatments L5 and L0, respectively). Within each trial, a batch of piglets was studied until slaughter. In trial 1, adipose cell development and total lipid content were determined on some pigs at weaning (n = 6/treatment) and at slaughter in dorsal subcutaneous adipose tissue (n = 13/group at least) and in muscle (n = 46/group at least). Piglets' birth weight was not affected by treatment in trial 1. Survival rates at birth and after 24 h of life were higher in treatment GL5 (4.0% v. 7.5% stillborn piglets in GL0 treatment, P < 0.05; 8.7% v. 12.6% of piglets alive at 24 h of age died in treatment GL0, P = 0.06). Subsequently, overall survival rate until weaning was higher in treatment GL5 (81.4% v. 75.7% of total born piglets, P = 0.03), but litter size at weaning was not significantly affected (11.3). Litter growth rate before weaning was increased when a fat-enriched diet was provided during gestation and lactation (+140 g/day per litter; P < 0.01) and to a lower extent when provided only after farrowing (+90 g/day; P < 0.05). Energy supply through fat did not decrease the mobilisation of the sow's body reserve and backfat thickness loss was even higher with treatment GL5 (P < 0.05). After weaning, pigs' average daily gain, feed : gain ratio and carcass lean content were not affected by the energy source supplied before and/or after farrowing. At weaning, the number of adipose cells in the dorsal subcutaneous adipose tissue and in the Longissimus dorsi muscle was higher in the GL5 pigs. Muscle lipid content at weaning did not differ between treatments, but it was higher at slaughter, around 110 kg, in the GL5 pigs (3.46% v. 2.58%, P < 0.001).     

Spatial and developmental regulation of leptin in fetal sheep

To better understand the biology of leptin during prenatal life, the developmental and spatial regulation of leptin was studied in ovine fetuses. Fetal plasma leptin increased steadily between days 40 and 143 postcoitus (PC), but it was unrelated to fetal weight or placental weight at day 135 PC. Leptin gene expression was detected in fetal brain and liver during most of gestation and in fetal adipose tissue after day 100 PC. At day 130 PC, expression in fetal perirenal adipose tissue was approximately 10% of maternal expression. In contrast, leptin gene expression was never detected in the placenta and other uteroplacental tissues. When ewes were fed 55% of requirements between days 122 and 135 PC, fetal plasma leptin remained constant despite acute reduction in maternal concentration. We conclude that fetal plasma leptin originates mostly from nonadipose tissue in early pregnancy and, in addition, from fetal adipose tissue near term. The role of fetal plasma leptin remains uncertain given the lack of nutritional regulation and association with fetal growth.     

Effect of maternal dietary fat on skeletal muscle cellularity and satellite cell content of the porcine fetus at 110 days of gestation

Crossbred gilts and sows were fed isocaloric diets that contained 0, 2.3, 12.8 or 29.7% poultry fat beginning at day 80 of gestation. At day 110 of gestation, fetuses were removed by Caesarean section. Maternal dietary fat did not influence fetal weight, sartorius muscle weight, length, composition, cellularity or satellite cell content. It was concluded that feeding diets high in fat during the last trisemester as exercised in this study did not influence the satellite cell content or cellularity of skeletal muscle.     

High and Low Protein∶ Carbohydrate Dietary Ratios during Gestation Alter Maternal-Fetal Cortisol Regulation in Pigs

Imbalanced maternal nutrition during gestation can cause alterations of the hypothalamic-pituitary-adrenal (HPA) system in offspring. The present study investigated the effects of maternal low- and high-protein diets during gestation in pigs on the maternal-fetal HPA regulation and expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) and c-fos mRNAs in the placenta and fetal brain. Twenty-seven German Landrace sows were fed diets with high (HP, 30%), low (LP, 6.5%) or adequate (AP, 12.1%) protein levels made isoenergetic by varying the carbohydrate levels. On gestational day 94, fetuses were recovered under general anesthesia for the collection of blood, brain and placenta samples. The LP diet in sows increased salivary cortisol levels during gestation compared to the HP and AP sows and caused an increase of placental GR and c-fos mRNA expression. However, the diurnal rhythm of plasma cortisol was disturbed in both LP and HP sows. Total plasma cortisol concentrations in the umbilical cord vessels were elevated in fetuses from HP sows, whereas corticosteroid-binding globulin levels were decreased in LP fetuses. In the hypothalamus, LP fetuses displayed an enhanced mRNA expression of 11β-HSD1 and a reduced expression of c-fos. Additionally, the 11β-HSD2 mRNA expression was decreased in both LP and HP fetuses. The present results suggest that both low and high protein∶carbohydrate dietary ratios during gestation may alter the expression of genes encoding key determinants of glucocorticoid hormone action in the fetus with potential long-lasting consequences for stress adaptation and health.     

Endocrine Regulation of Fetal Adipose Tissue Metabolism in the Pig: Interaction of Porcine Growth Hormone and Thyroxine

HAUSMAN, D.B., G.J. HAUSMAN, AND R.J. MARTIN. Endocrine regulation of fetal adipose tissue metabolism in the pig: interaction of porcine growth hormone and thyroxine. Obes Res. 1999;7:76–82. Objective : This study tested the hypothesis that combined treatment of thyroxine (T₄) and growth hormone (GH) could normalize cellular and metabolic aspects of adipose tissue development of hypophysectomized fetal pigs. Research Methods and Procedures : On day 70 of gestation, pig fetuses were hypophysectomized by microcauterization or remained intact. Hypophysectomized fetuses remained untreated or were treated from day 90 to day 105 of gestation with T₄, GH, or a combination of both hormones. Results : Body weights were unaffected by hypophysectomy or hormone treatment. De novo lipogenesis in subcutaneous adipose tissue was increased 10-fold by hypophysectomy, consistent with our previous results. This increase was abolished by GH treatment in the hypophysectomized fetuses. In contrast, T₄ treatment of the hypophysectomized fetuses resulted in a 12-fold further increase in adipose tissue lipogenesis, an effect that was negated by concomitant administration of GH. Lipolytic response to isoproterenol was decreased by hypophysectomy, unaffected by GH treatment, and restored to intact values by T₄ or by T₄+GH treatment in the hypophysectomized fetuses. Discussion : In contrast to T₄, GH does not influence serum insulin-like growth factor-I or adipose tissue lipolysis, but decreases lipogenesis in the fetal pig. However, replacing both T₄ and GH normalized hypophysectomized fetuses to a greater extent than either GH or T₄ alone. Thus, any influence of thyroid hormones on stimulating adipose tissue lipogenesis in the developing fetal pig may be normally counterregulated by pituitary-derived growth hormone.     

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.