Function and dysfunction of fatty acid mobilization: a review

Western populations have a growing obesity epidemic due in part to excessive nutrient intake from high-fat diets, which are increasingly common. Overindulgence of nutrients is associated with a greater incidence of metabolic dysfunction and a greater risk for obesity, diabetes, hypertension, and other metabolic disorders that lower quality of life. Research in humans and animal models has improved our understanding of how excess circulating free fatty acids negatively impact the ability of muscle and other tissues to regulate nutrient uptake and utilization. It is generally accepted by the scientific community that excess circulating fatty acids lead to insulin resistance, but there is little clarity regarding the underlying mechanisms. In the present review, we will outline the current understanding of the characteristics associated with fatty acid mobilization and fatty acid utilization within specific tissues. We will also discuss the potential mechanistic role of hyperlipidemia on metabolic dysfunction associated with type 2 diabetes

Function and dysfunction of fatty acid mobilization: a review.

Western populations have a growing obesity epidemic due in part to excessive nutrient intake from high-fat diets, which are increasingly common. Overindulgence of nutrients is associated with a greater incidence of metabolic dysfunction and a greater risk for obesity, diabetes, hypertension, and other metabolic disorders that lower quality of life. Research in humans and animal models has improved our understanding of how excess circulating free fatty acids negatively impact the ability of muscle and other tissues to regulate nutrient uptake and utilization. It is generally accepted by the scientific community that excess circulating fatty acids lead to insulin resistance, but there is little clarity regarding the underlying mechanisms. In the present review, we will outline the current understanding of the characteristics associated with fatty acid mobilization and fatty acid utilization within specific tissues. We will also discuss the potential mechanistic role of hyperlipidemia on metabolic dysfunction associated with type 2 diabetes

The Effect of Cow Udder Score on Subsequent Calf Performance in the Nebraska Sandhills

Cow records were evaluated over a 5-yr period to investigate how cow udder score affected calf growth and carcass performance. Cows from 2 calving herds, March and May, were classified as bad or good based on udder scores recorded at calving. Calves suckling dams with bad udders performed similarly during the pre-weaning period to good udder counterparts, with no differences in overall steer feedlot performance between udder groups. However, steers suckling good udder cows had heavier carcass weights and greater back fat thickness

Effect of Age of Dam on Heifer Progeny Performance

Cattle records were gathered and evaluated over a 12- yr period to investigate how cow age impacts heifer progeny growth and reproductive performance. Cow records from March and May calving herds, were categorized into young, moderate, and old groups based on their age at calving each year in the herd. Heifer calves born to young cows had lighter body weight at birth and adjusted 205- d BW than heifers from moderate and old cows. Heifer pre-breeding BW and pregnancy determination BW were not influenced by dam age. However, age of dam does impact the percentage of heifers to reach puberty prior to the start of breeding with no differences in percentage of heifers who calved within the first 21 d of calving in the subsequent calving season and pregnancy rates. Average number of calf crops from heifer progeny was different among all age of dam groups with young dams having more calves. Results from this study suggest older cows have a positive influence on growth and pre-breeding puberty status in female progeny during heifer development. Heifer progeny from young dams, however, had increased calf crops and longevity within the cowherd

Maternal inflammation at 0.7 gestation in ewes leads to intrauterine growth restriction and impaired glucose metabolism in offspring at 30 d of age

Fetal programming associated with intrauterine growth restriction (IUGR) leads to lifelong deficits in growth and metabolic function (Hales and Barker, 2013). IUGR arises when fetuses respond to poor in utero conditions by developing adaptations that repartition nutrients to critical tissues and away from skeletal muscle (Yates et al., 2012, 2018). This fetal programming is beneficial in utero but leads to persistent reductions in muscle mass and glucose homeostasis in offspring (DeFronzo et al., 1981). Recent studies by our laboratory in sheep and rats demonstrate that maternal inflammation during gestation induces fetal inflammatory adaptations that impair growth and disrupt muscle glucose metabolism (Cadaret et al., 2017, 2018). IUGR fetal skeletal muscle exhibits indicators of enhanced inflammatory sensitivity, which could disrupt glucose uptake and oxidation (Yates et al., 2016; Cadaret et al., 2018). Enhanced inflammatory responsiveness would help explain growth and metabolic deficits observed in IUGR offspring. We hypothesize that fetal programming induced by maternal inflammation persists in offspring and contributes to impaired growth and glucose metabolism at 30 d. Therefore, the objective of this study was to determine whether sustained maternal inflammation induced by bacterial endotoxin at 0.7 gestation leads to fetal programming that contributes to deficits in growth and glucose metabolism in offspring

Deficits in growth, muscle mass, and body composition following placental insufficiency-induced intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation

Low birthweight in livestock results from stress-induced intrauterine growth restriction (IUGR; Yates et al., 2018). IUGR fetuses exhibit diminished muscle growth that persists in the neonatal stage, leading to asymmetric body composition and decreased weight gain (Cadaret et al., 2019). Ultimately, low birthweight diminishes yield and carcass merit at harvest (Greenwood et al., 2000), making effective postnatal treatment strategies to improve IUGR growth outcomes necessary. In this study, we examined the benefits of injecting the β2 agonist clenbuterol daily to target adrenergic adaptations that we previously observed in IUGR muscle (Posont et al., 2018; Yates et al., 2018). We hypothesized that IUGRinduced growth deficits would persist at the juvenile stage, manifesting in inferior body composition and carcass traits. We also postulated that clenbuterol would at least partially recover growth and body symmetry. Our objective was to test this hypothesis by assessing growth metrics and body composition in IUGR-born lambs hand-reared to 60 d of age and supplemented daily with injectable clenbuterol

Effect of Supplemental Protein and Glucogenic Precursors on Digestibility and Energy Metabolism

A metabolism study was conducted to evaluate the impact of increasing levels of glucogenic precursors on diet digestibility and acetate clearance. Four supplementation strategies containing 0, 30, 40, and 70 g of supplemental glucogenic potential were supplied to a basal diet of bromegrass hay. Addition of glucogenic potential in the form of rumen undegradable protein improved dry matter, organic matter, and acid detergent fiber digestibility efficiency of acetate utilization in growing lambs fed moderate- quality hay. However, no additive effect of supplementing propionate salts and rumen undegradable protein were observed in this study. Th is would suggest that rumen undegradable protein requirements must be met to observe effects from increasing levels of glucogenic potential

Maternal inflammation at 0.7 gestation in ewes leads to intrauterine growth restriction and impaired glucose metabolism in offspring at 30 d of age

Fetal programming associated with intrauterine growth restriction (IUGR) leads to lifelong deficits in growth and metabolic function (Hales and Barker, 2013). IUGR arises when fetuses respond to poor in utero conditions by developing adaptations that repartition nutrients to critical tissues and away from skeletal muscle (Yates et al., 2012, 2018). This fetal programming is beneficial in utero but leads to persistent reductions in muscle mass and glucose homeostasis in offspring (DeFronzo et al., 1981). Recent studies by our laboratory in sheep and rats demonstrate that maternal inflammation during gestation induces fetal inflammatory adaptations that impair growth and disrupt muscle glucose metabolism (Cadaret et al., 2017, 2018). IUGR fetal skeletal muscle exhibits indicators of enhanced inflammatory sensitivity, which could disrupt glucose uptake and oxidation (Yates et al., 2016; Cadaret et al., 2018). Enhanced inflammatory responsiveness would help explain growth and metabolic deficits observed in IUGR offspring. We hypothesize that fetal programming induced by maternal inflammation persists in offspring and contributes to impaired growth and glucose metabolism at 30 d. Therefore, the objective of this study was to determine whether sustained maternal inflammation induced by bacterial endotoxin at 0.7 gestation leads to fetal programming that contributes to deficits in growth and glucose metabolism in offspring

Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction

Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (IUGR) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the β2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater (p \u3c 0.05) circulating TNF, IL-6, and non-esterified fatty acids, increased (p \u3c 0.05) intramuscular glycogen, reduced (p \u3c 0.05) circulating IGF-1, hindlimb blood flow, glucose-stimulated insulin secretion, and muscle glucose oxidation. Daily clenbuterol fully recovered (p \u3c 0.05) circulating TNF, IL-6, and nonesterified fatty acids, hindlimb blood flow, muscle glucose oxidation, and intramuscular glycogen. Glucose-stimulated insulin secretion was partially recovered (p \u3c 0.05) in clenbuterol-treated IUGR lambs, but circulating IGF-1 was not improved. Circulating triglycerides and HDL cholesterol were elevated (p \u3c 0.05) in clenbuterol-treated IUGR lambs, despite being normal in untreated IUGR lambs. We conclude that deficient β2 adrenergic regulation is a primary mechanism for several components of metabolic dysfunction in IUGR-born offspring and thus represents a potential therapeutic target for improving metabolic outcomes. Moreover, benefits from the β2 agonist were likely complemented by its suppression of IUGR-associated inflammation