Obesity in pregnancy: problems and potential solutions.

Recent years have witnessed an increase in the prevalence of maternal obesity during pregnancy in the United States and worldwide. Obese women have increased risks for gestational problems, such as diabetes, hypertension, and pre-eclampsia. Further, gestational obesity can adversely impact fetal growth and result in macrosomia, congenital abnormalities, and even fetal death. Measures must be taken to reduce maternal adiposity, as even a modest weight loss during pregnancy is beneficial for the health of mothers and fetus. Calorie restriction and moderate exercise are proven safe methods of stopping weight gain and/or inducing white-fat loss in these subjects. Additionally, therapeutic drugs that activate the AMP-activated protein kinase signaling pathway may be effective in ameliorating pathological conditions in obese patients. Finally, dietary supplementation with L-arginine or its effective precursor (L-citrulline) may be beneficial for managing overweight or obese gestating women by reducing white-fat accretion. Because of ethical concerns over human studies, animal models (e.g., sheep, pigs, baboons, rats, and mice) are warranted to test novel hypotheses with enormous biological significance and clinical applications.

Proline and hydroxyproline metabolism: implications for animal and human nutrition.

Proline plays important roles in protein synthesis and structure, metabolism (particularly the synthesis of arginine, polyamines, and glutamate via pyrroline-5-carboxylate), and nutrition, as well as wound healing, antioxidative reactions, and immune responses. On a per-gram basis, proline plus hydroxyproline are most abundant in collagen and milk proteins, and requirements of proline for whole-body protein synthesis are the greatest among all amino acids. Therefore, physiological needs for proline are particularly high during the life cycle. While most mammals (including humans and pigs) can synthesize proline from arginine and glutamine/glutamate, rates of endogenous synthesis are inadequate for neonates, birds, and fish. Thus, work with young pigs (a widely used animal model for studying infant nutrition) has shown that supplementing 0.0, 0.35, 0.7, 1.05, 1.4, and 2.1% proline to a proline-free chemically defined diet containing 0.48% arginine and 2% glutamate dose dependently improved daily growth rate and feed efficiency while reducing concentrations of urea in plasma. Additionally, maximal growth performance of chickens depended on at least 0.8% proline in the diet. Likewise, dietary supplementation with 0.07, 0.14, and 0.28% hydroxyproline (a metabolite of proline) to a plant protein-based diet enhanced weight gains of salmon. Based on its regulatory roles in cellular biochemistry, proline can be considered as a functional amino acid for mammalian, avian, and aquatic species. Further research is warranted to develop effective strategies of dietary supplementation with proline or hydroxyproline to benefit health, growth, and development of animals and humans.

Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health.

Over the past 20 years, growing interest in the biochemistry, nutrition, and pharmacology of L-arginine has led to extensive studies to explore its nutritional and therapeutic roles in treating and preventing human metabolic disorders. Emerging evidence shows that dietary L-arginine supplementation reduces adiposity in genetically obese rats, diet-induced obese rats, finishing pigs, and obese human subjects with Type-2 diabetes mellitus. The mechanisms responsible for the beneficial effects of L-arginine are likely complex, but ultimately involve altering the balance of energy intake and expenditure in favor of fat loss or reduced growth of white adipose tissue. Recent studies indicate that L-arginine supplementation stimulates mitochondrial biogenesis and brown adipose tissue development possibly through the enhanced synthesis of cell-signaling molecules (e.g., nitric oxide, carbon monoxide, polyamines, cGMP, and cAMP) as well as the increased expression of genes that promote whole-body oxidation of energy substrates (e.g., glucose and fatty acids) Thus, L-arginine holds great promise as a safe and cost-effective nutrient to reduce adiposity, increase muscle mass, and improve the metabolic profile in animals and humans.