Fighting Fat With Fat: n-3 Polyunsaturated Fatty Acids and Adipose Deposition in Broiler Chickens

Modern broiler chickens are incredibly efficient, but they accumulate more adipose tissue than is physiologically necessary due to inadvertent consequences of selection for rapid growth. Accumulation of excess adipose tissue wastes feed in birds raised for market, and it compromises well-being in broiler-breeders. Studies driven by the obesity epidemic in humans demonstrate that the fatty acid profile of the diet influences adipose tissue growth and metabolism in ways that can be manipulated to reduce fat accretion. Omega-3 polyunsaturated fatty acids (n-3 PUFA) can inhibit adipocyte differentiation, induce fatty acid oxidation, and enhance energy expenditure, all of which can counteract the accretion of excess adipose tissue. This mini-review summarizes efforts to counteract the tendency for fat accretion in broilers by enriching the diet in n-3 PUFA.

A Role for the Pregravid Maternal Milieu in the Intergenerational Transmission of Obesity

Objectives Maternal obesity increases the risk for adverse pregnancy and offspring outcomes; however, with large heterogeneity. We hypothesize that in mothers with obesity, the heterogeneity of offspring adiposity is due to prolonged exposure to excess maternal substrates, namely glucose and triglycerides, which promote fetal fat accretion. The aims of this prospective observational study were to 1) examine the maternal metabolic milieu in pregnant women with metabolically unhealthy obesity, MUO and metabolically healthy obesity, MHO; and 2) identify if these maternal metabolic phenotypes in women with obesity influence infant adiposity. Methods During early pregnancy, 51 women with obesity were classified to have MUO (n = 9) or MHO (n = 13) based on the presence of zero (MHO) or ≥ 2 (MUO) risk factors for metabolic syndrome (SBP > 130 or DBP > 85, HDL < 50 mg/dL, LDL ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, and glucose ≥ 100 mg/dL). Area under the pregnancy concentration curve (AUC) for glucose and triglycerides, gestational weight gain (GWG), fat accretion, and energy intake and expenditure from early (13–16 wks), mid (24–27 wks) to late (35–37 wks) pregnancy and infant fat mass were compared between groups. Results Compared to women with MHO, women with MUO were not different with respect to maternal BMI, GWG, fat accretion, energy and macronutrient intake, and energy expenditure. In both groups, maternal substrates changed similarly from ∼13 to ∼37 weeks of pregnancy, however MUO resulted in greater pregnancy AUC for glucose (+2169.7 ± 381.5 p < 0.001 mg/dL · day) and triglycerides (+12,210.5 ± 3916.1 mg/dL · day, p < 0.001). The offspring of women with MHO had significantly lower birth weight (−620.8 ± 204.6 g, p = 0.01), body fat percentage (−5.8 ± 2.1%, p = 0.02), and total fat mass (−268.8 ± 88.4 g, p = 0.01). Conclusions Differing obesity phenotypes in pregnancy may explain the heterogeneity of offspring adiposity. Metabolically unhealthy obesity resulted in a more prolonged exposure of fetal fat promoting substrates and increased adiposity at birth. This study identifies a population of women with obesity most in need of prenatal interventions and suggests that obesity phenotypes need to be considered when evaluating intervention effect on offspring outcomes. Funding Sources R01DK099175.

Greater Maternal Dietary Fiber Intake Protects Against Infant Central Fat Accretion Related to High Maternal Fructose Intake

Objectives Greater maternal fructose intake is linked to greater offspring fat accrual, while dietary fiber intake is related to lower weight gain and a more favorable adipose tissue distribution. However, data are lacking investigating these relationships in the especially critical time of pregnancy and early infancy. We explored the relationships between maternal fructose and fiber intake on early offspring adipose tissue accrual. Methods This is a secondary analysis using data from a prenatal DHA supplementation trial (ADORE HD083292). At enrollment (12–16 wks), women completed the DHQ II food frequency questionnaire. ADORE mothers were invited to enroll in the GAINS infant follow up study (DK118220). Infant skinfolds were assessed two weeks and six months at three central sites (suprailiac, subscapular, flank) and three peripheral sites (biceps, triceps, thigh). Median splits were calculated for maternal fructose and total dietary fiber intake (< 50th percentile, ≥50th percentile). An ANCOVA assessed the main effects of maternal fructose and fiber intake on infant fat accrual (central and peripheral). Results Data were available on n = 61 infants. For the change in infant central FM, a significant interaction (p = 0.034) was found between maternal fructose intake and dietary fiber intake. No effect of fiber was found in offspring exposed to low fructose intake. However, in offspring exposed to high fructose intake during pregnancy, exposure to high maternal dietary fiber intake was related to lower central FM accrual (high fiber intake: 4.2 mm vs. low fiber intake 6.9 mm; p = 0.016). No significant main effects or interaction was detected for the change in peripheral FM. Conclusions In offspring exposed to greater maternal fructose consumption during pregnancy, greater maternal intake of dietary fiber was related to lower early offspring central fat accretion. Interventions targeting to decrease maternal fructose consumption and increase maternal dietary fiber intake may positively impact offspring fat accretion. Funding Sources NIH Awards R01 HD083292 and R01 DK118220.

Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Hepatic Fat Accretion and Energy and Fatty Acids Profile of Fetal Tissues

Maternal supplementation with hydroxytyrosol, a polyphenol present in olive leaves and fruits, is a highly promising strategy to improve the oxidative and metabolic status of fetuses at risk of intrauterine growth restriction, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine whether hydroxytyrosol, by preventing lipid peroxidation, may influence the fat accretion and energy homeostasis in the liver, as well as the fatty acid composition in the liver and muscle. The results indicate that hydroxytyrosol treatment significantly decreased the energy content of the fetal liver, without affecting fat accretion, and caused significant changes in the availability of fatty acids. There were significant increases in the amount of total polyunsaturated fatty acids, omega-3 and omega-6, which are highly important for adequate fetal tissue development. However, there were increases in the omega-6/omega-3 ratio and the desaturation index, which make further studies necessary to determine possible effects on the pro/anti-inflammatory status of the fetuses.

Maternal Dicer Knockout Impairs Growth and Gut Health in Nursing Wild-type Pups in Mice (P11-137-19)

Objectives Background: Dicer catalyzes microRNA biogenesis. Administration of tamoxifen to heterozygous Dicer conditional knockout (KO) mice (Dicer + /-) deletes one Dicer allele (Dicer KO). Nanoparticles (exosomes) transfer microRNAs from donor cells to recipient cells. Humans absorb exosomes and microRNA cargos from milk. MicroRNAs regulate the expression of 60% of mammalian genes. Objectives: Assess whether the loss of microRNA biogenesis in lactating Dicer KO dams impairs growth and gut health in nursing wild-type pups. Methods Newborn pups from wild-type (WT) C57BL/6 breeders were fostered to synchronized Dicer + /- dams. Dams were injected with tamoxifen or vehicle (control). Additional controls included WT pups fostered to WT dams injected with tamoxifen or vehicle. Body weight gain and milk consumption were measured at timed intervals up to 21 days when pups were euthanized. Body fat accretion was assessed using NMR. Sections of the gastrointestinal tract were evaluated by histology analyses. The unpaired t-test was used for statistical analysis (tamoxifen vs. vehicle); P < 0.05 was considered statistically significant. Results Body weight and fat accretion in male and female pups nursed by Dicer KO dams was significantly lower than in vehicle controls at age 3 weeks (Figs. 1 and 2). Histology assessment revealed villous atrophy in the small intestine from pups nursed by Dicer KO dams compared to vehicle controls at age 3 weeks (Figs. 3–5). Tamoxifen administration did not elicit phenotypes in wild-type pups nursed by wild-type dams (not shown). Milk consumption was not significantly different between pups nursed by Dicer KO dams and controls (not shown). Conclusions Loss of microRNA biogenesis in lactating Dicer KO dams impairs growth and gut health in nursing wild-type pups. The quality of milk secreted by Dicer KO dams remains to be assessed. Funding Sources NIFA, NIH, Gerber Foundation, Gates Foundation, PureTech, Inc. and USDA Hatch and Multistate. J.Z. is a consultant for PureTech. Supporting Tables, Images and/or Graphs