Relationship of ANGPTL6 With Neonatal Glucose Homeostasis and Fat Mass Is Disrupted in Gestational Diabetic Pregnancies.

CONTEXT: Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine, which, in animal studies, improves insulin sensitivity and increases energy expenditure to counteract insulin resistance. OBJECTIVE: Evaluate in a human population, the role of serum ANGPTL6 in gestational diabetes mellitus (GDM) or its presence in fetal circulation. RESEARCH DESIGN AND METHODS: A total of 190 women (115 controls and 75 GDM) and their offspring were studied. Insulin, glucose, ANGPTL6, retinol binding protein 4 (RBP4), and retinol, as well as leptin and adiponectin, were determined in maternal serum obtained at term and from umbilical artery blood at delivery. RESULTS: At term, pregnant women with GDM showed higher serum concentrations of ANGPTL6, insulin, homeostatic model assessment, and apo-RBP4 (free RBP4) than controls but not of glucose, which remained similar in both groups. Also, in arterial cord serum, ANGPTL6 concentration was increased in GDM neonates with respect to the control group (201 ±â€…12 ng/mL vs 119 ±â€…8 ng/mL, respectively). No effect of maternal insulin treatment of some GDM mothers in neonates of either sex on ANGPTL6 levels was observed. In GDM, circulating ANGPTL6 showed no correlation with glucose or insulin concentration or with neonatal adiposity. However, in control pregnancies, the variation in glucose concentration was positively correlated with ANGPTL6 concentration, both in maternal and in cord samples, and cord ANGPTL6 was negatively correlated with neonatal fat mass. Furthermore, in control pregnant women, serum concentrations of ANGPTL6 and apo-RBP4 were negatively correlated. CONCLUSION: Serum ANGPTL6 levels are associated with maternal glucose homeostasis and fetal adiposity in normal pregnancy. ANGPTL6 levels in maternal and cord serum GDM pregnancy at term are increased, although its mechanism and physiological role are unknown yet.

Reduction of litter size during lactation in rats greatly influences fatty acid profiles in dams.

This study aimed to determine in lactating rats how fatty acid profiles are affected by litter size. On day 2 after parturition, litters of lactating rats were adjusted to a normal litter size of 9 pups/dam (NL) or to a small litter of 4 pups/dam (SL), and dams were studied at day 21 of lactation. Plasma glucose, insulin, and docosahexaenoic acid (DHA) concentrations were higher in SL than in NL dams, whereas the concentrations of most other fatty acids, triacylglycerols (TAG), and non-esterified fatty acids were lower in the SL dams. In the liver, the concentration of TAG was lower in SL than in NL dams as was the concentration of most fatty acids, with the exception of stearic acid (STA), arachidonic acid (ARA), and DHA concentrations that were higher in SL. Both plasma and liver Δ9 desaturase indices were lower in SL than in NL dams, whereas both Δ5 and Δ6 desaturase indices were higher in SL dams. In the liver, the expression of acetyl CoA carboxylase was lower in SL than in NL dams, and among the different adipose tissue depots, only mesenteric adipose tissue showed a higher concentration of most fatty acids in SL than in NL dams. It is proposed that reduction of litter size during lactation decreases liver lipogenesis de novo, although the synthesis of long-chain polyunsaturated fatty acids from their corresponding precursors increases, and lipolytic activity in mesenteric adipose tissue decreases probably as result of increased insulin responsiveness.

Dietary fish oil supplementation during early pregnancy in rats on a cafeteria-diet prevents fatty liver in adult male offspring.

We studied in rats the effects of cafeteria diet (CD) supplemented (or not) with fish oil (FO) during just the first 12 days of pregnancy, or during the whole of pregnancy and lactation in 14-month old offspring. Female rats were given standard diet (STD) or CD and after mating some animals remained on STD or CD; for some CD rats the diet was supplemented with 8.78% FO. After 12 days, half of the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. From weaning all offspring were given STD. The adiposity index of male offspring of CD dams increased but was normal in CD-FO males. Plasma triacylglycerols (TAG) and individual fatty acid concentrations were similar among the groups. Liver total lipids, TAG, fatty acid concentrations, Δ9-desaturase indices and the mRNA expression of fatty acid synthase were higher in male offspring of CD than in those of STD; most of these differences disappeared in male offspring of CD-FO12 and CD-FO dams. Female offspring showed smaller changes. Thus, a moderate supplement with FO during just the first half of gestation or during pregnancy and lactation in rats on CD decreases the liver steatosis in male adult offspring.

Influence of cafeteria diet and fish oil in pregnancy and lactation on pups' body weight and fatty acid profiles in rats.

PURPOSE: The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring. METHODS: Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. RESULTS: At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ(5) and Δ(6) desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups. CONCLUSIONS: The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ(5) and Δ(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.

Supplementing diet with blackberry extract causes a catabolic response with increments in insulin sensitivity in rats.

Blackberry (Rubus sp.) fruit has a high content of anthocyanins, but its health benefits have not been sufficiently explored in healthy individuals. Thus, the aim of the study was to determine the effects of blackberry extract on lipid and glucose variables in female and male rats. Sprague Dawley rats were given a standard pellet (SD) or cafeteria (CD) diet supplemented (SD+R and CD+R) or not with Rubus extract for 80 days. Female rats given SD+R had lower body and liver weights than SD females; both sexes given SD+R showed lower plasma glucose and insulin, higher plasma NEFA, glycerol and 3-hydroxybutyrate, and higher liver concentration of triacylglycerols than SD rats. The homeostasis model of insulin resistance (HOMA) was lower in SD+R rats than in SD rats, but higher in CD rats. No effects of Rubus extract were observed in CD rats. In conclusion, Rubus extract, in rats given SD, decreased glycemia and increased insulin sensitivity. It also increased lipid breakdown in adipose tissue. The effects were greater in females than in males. No effect was seen in rats given CD, probably as a result of their high insulin resistance.

Maternal consumption of trans-fatty acids during the first half of gestation are metabolically available to suckled newborn rats.

Dietary trans-fatty acids (t-FA) during pregnancy have adverse effects on growth and development. To determine the effect of dietary t-FA during just the first half of pregnancy, rats were given a diet containing 8 % hydrogenated peanut oil and 2 % olive oil (PO) and compared to rats given a diet containing 10 % olive oil (OO). After 12 days all rats were fed standard diet and were studied at days 12 or 20 of pregnancy or days 1 or 6 postpartum. At day 12 of pregnancy there were small differences in the plasma and lumbar adipose tissue fatty acid profiles and elaidic acid [18:1(n-9)t] was present in the PO group. From day 12 to 20 of pregnancy, plasma non-esterified fatty acids, glycerol, triacylglycerols (TAG) and most individual fatty acids increased more in PO than in OO. At day 20 of pregnancy in the PO group most plasma elaidic acid appeared as plasma TAG and was also present in the mammary gland, to decline in both sites at day 1 postpartum. Elaidic acid concentration was low in the plasma of 20-day fetuses, increased in 1-day newborns declining at day 6. Thus t-FA, eaten during early pregnancy, accumulated in maternal adipose tissue and were released during late pregnancy to be taken up by the mammary gland becoming available to the newborns during suckling.

Fatty acid composition of the maternal diet during the first or the second half of gestation influences the fatty acid composition of sows' milk and plasma, and plasma of their piglets.

Dietary supplements of olive oil (OO) or fish oil (FO) during the first (G1: day 1-60) or second half of gestation (G2: day 60 to term, day 115) were offered to pregnant sows. The proportion of fatty acids in milk and plasma were determined by gas chromatography. When supplements were given during G1, the proportions of oleic acid (OA) and arachidonic acid (AA) in the plasma were higher in the OO group than in the FO group, whereas docosahexaenoic acid (DHA) was higher in the latter group at day 56 of gestation. These differences in plasma DHA were still apparent at day 7 of lactation. Similarly, DHA was also higher in the colostrum and milk on days 3 and 21 of lactation and in the plasma of piglets from FO dams compared to the OO group, whereas AA was lower. When the FO supplement was given during G2, AA was lower and DHA higher in the plasma at day 105 of gestation and at day 7 of lactation compared with the OO group. Likewise, DHA was greater in FO than in OO animals during lactation in colostrum and in milk on days 3 and 21 of lactation, and in 3-day old suckling piglets plasma, whereas AA was lower in these animals. Thus, maternal adipose tissue plays an important role in the storage of dietary long-chain polyunsaturated fatty acids (LCPUFA) during G1. They are mobilized around parturition for milk synthesis, and an excess of dietary n-3 LCPUFA decreases the availability of AA in suckling newborns.

Effects of lipid-supplemented total parenteral nutrition on fatty liver disease in a premature neonatal piglet model.

BACKGROUND: Routine total parenteral nutrition (TPN) in neonatal care can result in hepatic dysfunction in 40-60% of patients, most commonly as fatty liver, but little work has been conducted on the underlying mechanisms causing hepatic dysfunction. OBJECTIVE: To use a piglet model for the premature human neonate on TPN, supplemented with lipid emulsions, to investigate hepatic responses. METHOD: Piglets were delivered 2 days prematurely. Six control piglets were fed enterally (E), whilst twelve animals were maintained on TPN. TPN piglets received the standard TPN solution plus the lipid emulsion as either ClinOleic(R) (C, n = 6) or Intralipid(R) (I, n = 6). Hepatic lipid content and the fatty acid composition of liver triacylglyercol (TAG) as well as hepatic lipase (HL) activity were determined. Lipoprotein lipase (LPL) activity was measured in the liver, muscle and adipose tissue. The plasma concentrations of choline, bilirubin, TAG and non-esterified fatty acids (NEFA) were also measured. RESULTS: Liver lipid was significantly increased in piglets on TPN and the tissue fatty acid profiles reflected the lipid emulsion. HL and LPL activities were reduced in liver but LPL increased in adipose tissue during TPN. Plasma concentrations of choline, bilirubin, TAG and NEFA were similar across the treatments. CONCLUSIONS: The results suggest fatty liver occurs in neonates receiving TPN and the source of the accumulated lipid appears to be the lipid emulsion used. The factors regulating lipase activity during TPN require further study. The piglet can be used as a model for neonatal TPN.

Influence of changes in dietary fatty acids during pregnancy on placental and fetal fatty acid profile in the rat.

To determine whether the composition of long-chain polyunsaturated fatty acids (PUFA) could be modified in the fetus by maternal dietary fatty acids, pregnant Sprague-Dawley rats were fed semipurified diets that differed only in the non-vitamin lipid component. The diets contained either 10 g palm, sunflower, olive or fish oil (FOD)/100 g diet. A total of 5-6 rats were studied in each group. At day 20 of gestation, corresponding to 1.5 days prior parturition, the fatty acids in maternal adipose tissue were closely related to the fatty acid composition in the corresponding diet. An important proportion of arachidonic acid (AA) appeared in maternal liver and plasma, although it was lower in the FOD than in the other groups. Except for saturated fatty acids, the proportion of individual fatty acids in the placenta correlated linearly with that in maternal plasma. Also, PUFA in fetal plasma and liver showed significant correlations with PUFA in maternal plasma. Again, AA showed the lowest proportion in the plasma and liver of the FOD group. Therefore, the maternal dietary fatty acid composition influences maternal and fetal plasma and tissue composition, and an increase in dietary omega-3 fatty acids decreases the amount of AA in maternal and fetal tissues.