Placental insufficiency (PI) prevents adequate delivery of nutrients to the developing fetus and creates a chronic state of hypoxemia and hypoglycemia. In response, the malnourished fetus develops a series of stress hormone-mediated metabolic adaptations to preserve glucose for vital tissues at the expense of somatic growth. Catecholamines suppress insulin secretion to promote glucose sparing for insulin-independent tissues (brain, nerves) over insulin-dependent tissues (skeletal muscle, liver, and adipose). Likewise, premature induction of hepatic gluconeogenesis helps maintain fetal glucose and appears to be stimulated by both norepinephrine and glucagon. Reduced glucose oxidation rate in PI fetuses creates a surplus of glycolysis-derived lactate that serves as substrate for hepatic gluconeogenesis. These adrenergically influenced adaptive responses promote in utero survival but also cause asymmetric intrauterine growth restriction and small-for-gestational-age infants that are at greater risk for serious metabolic disorders throughout postnatal life, including obesity and type II diabetes.

No abstract

Many animals convert β-carotene to retinol to meet their vitamin A (VA) requirement. However, this pathway is inefficient in many carnivores. This study quantified the plasma response to a single oral dose of [(2) H(8)]-β-carotene in adult domestic cats, including measurement of [(2) H(4)]-retinol derived from the dose. Cats were fed with either a control diet containing adequate VA (n = 5) or a VA-devoid diet (n = 5) for 28 days. An oral dose of either 5 mg/kg body weight (BW) (n = 4) or 10 mg/kg BW (n = 6) of [(2) H(8) ]-β-carotene was administered on day 28. Plasma samples were collected prior to dosing and at 6, 12, 24, 32, 48, 72, 120, 168 and 216 h post-dose. Plasma retinoids and β-carotene were measured using HPLC and [(2) H(4)]-retinol by GC-ECNCI-MS (gas chromatography/electron capture negative chemical ionization/mass spectrometry). β-carotene was undetectable in plasma prior to dosing. Post-dose, mean peak plasma β-carotene was 0.37 ± 0.06 nmol/ml at 9.0 ± 1.8 h following the dose, while [(2) H(4) ]-retinol peaked at 3.71 ± 0.69 pmol/ml at 55.2 ± 16.3 h. The ratio per cent of total area under the curve for [(2) H(4)]-retinol compared with the β-carotene response was 4.6 ± 2.6%. There was little effect of diet or dose on the β-carotene or [(2) H(4)]-retinol responses. The appearance of [(2) H(4)]-retinol in plasma indicates that cats are capable of converting β-carotene to active VA. Conversion efficiency was not calculated in this study, but it is likely inadequate to meet cats' VA requirement without the inclusion of preformed VA in the diet.