Insulin resistance, a hallmark of type 2 diabetes, is associated with oxidative stress. However, the role of reactive oxygen species or specific antioxidant enzymes in its development has not been tested under physiological conditions. The objective of our study was to investigate the impact of overexpression of glutathione peroxidase 1 (GPX1), an intracellular selenoprotein that reduces hydrogen peroxide (H₂O₂)in vivo, on glucose metabolism and insulin function. The GPX1-overexpressing (OE) and WT male mice (n= 80) were fed a selenium-adequate diet (0.4 mg/kg) from 8 to 24 weeks of age. Compared with the WT, the OE mice developed (P< 0.05) hyperglycemia (117 vs. 149 mg/dl), hyperinsulinemia (419 vs. 1,350 pg/ml), and elevated plasma leptin (5 vs. 16 ng/ml) at 24 weeks of age. Meanwhile, these mice were heavier (37 vs. 27 g,P< 0.001) and fatter (37% vs. 17% fat,P< 0.01) than the WT mice. At 30–60 min after an insulin challenge, the OE mice had 25% less (P< 0.05) of a decrease in blood glucose than the WT mice. Their insulin resistance was associated with a 30–70% reduction (P< 0.05) in the insulin-stimulated phosphorylations of insulin receptor (β-subunit) in liver and Akt (Ser⁴⁷³and Thr³⁰⁸) in liver and soleus muscle. Here we report the development of insulin resistance in mammals with elevated expression of an antioxidant enzyme and suggest that increased GPX1 activity may interfere with insulin function by overquenching intracellular reactive oxygen species required for insulin sensitizing.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways.

Feed protein supplements are one of the most expensive and limiting feed ingredients. This review offers a comprehensive analysis of how the expected expansion of animal production, driven by the rising world population and living standards for more animal-sourced foods, is creating a global shortage of feed protein supply. Because ruminants, chickens, and pigs contribute to 96% of the global supply of animal protein and aquaculture is growing fast, means of meeting the feed protein requirements of these species are elaborated. Geographic variation and interdependence among China, Europe, and North America in the demand and supply of feed protein are compared. The potential and current state of exploration into alternative feed proteins, including microalgae, insects, single-cell proteins, and coproducts, are highlighted. Strategic innovations are proposed to upgrade feed protein processing and assessment, improve protein digestion by exogenous enzymes, and genetically select feed-efficient livestock breeds. An overall successful and sustainable solution in meeting global feed protein demands will lead to a substantial net gain of human-edible animal protein with a minimal environmental footprint.

Glutathione peroxidase-1 (GPX1) represents the first identified mammalian selenoprotein, and our understanding in the metabolic regulation and function of this abundant selenoenzyme has greatly advanced during the past decade. Selenocysteine insertion sequence–associating factors, adenosine, and Abl and Arg tyrosine kinases are potent, Se-independent regulators of GPX1 gene, protein, and activity. Overwhelming evidences have been generated using the GPX1 knockout and transgenic mice for the in vivo protective role of GPX1 in coping with oxidative injury and death mediated by reactive oxygen species. However, GPX1 exerts an intriguing dual role in reactive nitrogen species (RNS)-related oxidative stress. Strikingly, knockout of GPX1 rendered mice resistant to toxicities of drugs including acetaminophen and kainic acid, known as RNS inducers. Intracellular and tissue levels of GPX1 activity affect apoptotic signaling pathway, protein kinase phosphorylation, and oxidant-mediated activation of NFκB. Data are accumulating to link alteration or abnormality of GPX1 expression to etiology of cancer, cardiovascular disease, neurodegeneration, autoimmune disease, and diabetes. Future research should focus on the mechanism of GPX1 in the pathogeneses and potential applications of GPX1 manipulation in the treatment of these disorders.

The rise in global population has led to explorations of alternative sources of energy and food. Because corn and soybean are staple food crops for humans, their common use as the main source of dietary energy and protein for food-producing animals directly competes with their allocation for human consumption. Alternatively, de-fatted marine microalgal biomass generated from the potential biofuel production may be a viable replacement of corn and soybean meal due to their high levels of protein, relatively well-balanced amino acid profiles, and rich contents of minerals and vitamins, along with unique bioactive compounds. Although the full-fatted (intact) microalgae represent the main source of omega-3 (n-3) polyunsaturated fatty acids including docohexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the de-fatted microalgal biomass may still contain good amounts of these components for enriching DHA/EPA in eggs, meats, and milk. This review is written to highlight the necessity and potential of using the de-fatted microalgal biomass as a new generation of animal feed in helping address the global energy, food, and environmental issues. Nutritional feasibility and limitation of the biomass as the new feed ingredient for simple-stomached species are elaborated. Potential applications of the biomass for generating value-added animal products are also explored.

Phytases are phosphohydrolytic enzymes that initiate stepwise removal of phosphate from phytate. Simple-stomached species such as swine, poultry, and fish require extrinsic phytase to digest phytate, the major form of phosphorus in plant-based feeds. Consequently, this enzyme is supplemented in these species’ diets to decrease their phosphorus excretion, and it has emerged as one of the most effective and lucrative feed additives. This chapter provides a comprehensive review of the evolving course of phytase science and technology. It gives realistic estimates of the versatile roles of phytase in animal feeding, environmental protection, rock phosphorus preservation, human nutrition and health, and industrial applications. It elaborates on new biotechnology and existing issues related to developing novel microbial phytases as well as phytase-transgenic plants and animals. And it targets critical and integrated analyses on the global impact, novel application, and future demand of phytase in promoting animal agriculture, human health, and societal sustainability.