Annual Review of Nutrition - Volume 20, 2000

The cloning of the G protein-coupled, extracellular calcium (Ca²⁺o)-sensing receptor (CaR) has identified a central mediator of the mechanism governing systemic Ca²⁺o homeostasis. This system enables organisms to adapt successfully to wide variations in dietary Ca²⁺o intake while maintaining near constancy of Ca²⁺o. Whereas discussions of Ca²⁺o homeostasis have generally focused on the key role of Ca²⁺o-elicited changes in parathyroid hormone secretion, the presence of the CaRs in effector tissues of this system enables direct regulation of processes (e.g. renal tubular Ca²⁺ reabsorption and possibly bone formation and resorption) that add additional layers of homeostatic control. As we understand more about how the CaR regulates these tissues, we may find that it participates in other processes relevant to mineral ion homeostasis, including the control of the 1-hydroxylation and activation of vitamin D3 or reabsorption of phosphate in the renal proximal tubule. Regardless, the remarkable sensitivity of the CaR to small changes in Ca²⁺o allows adjustments in the response of the Ca²⁺o homeostatic system to increases or decreases in the intake of dietary Ca²⁺, for instance, that cause barely detectable alterations in Ca²⁺o. Furthermore, the CaR likely participates in coordinating interactions among several different homeostatic control systems (including those for water, Mg²⁺o, Na⁺, extracellular volume, and/or blood pressure), despite the fact that these systems are often considered to function largely independently of mineral ion metabolism.

The major transcriptional factors involved in the adipogenic process include proteins belonging to the CCAAT/enhancer binding protein family, peroxisome proliferator-activated receptor γ, and adipocyte determination and differentiation dependent factor 1, also known as sterol regulatory element-binding protein 1. This process has been characterized with the aid of cell lines that represent various stages in the path of adipocyte commitment, ranging from pluripotent mesodermal fibroblasts to preadipocytes. Molecular analyses have led to a cascade model for adipogenesis based on timed expression of CCAAT/enhancer-binding proteins and peroxisome proliferator-activated receptor γ. Gene targeting and transgenic-mouse technologies, which allow the manipulation of endogenous genes for these transcription factors, have also contributed to the understanding of adipogenesis. This review aims to integrate this information to gain an understanding of the transcriptional regulation of fat cell formation.

Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular mortality when compared with individuals who abstain or who drink alcohol to excess. Researchers are working to explain this observation in molecular and nutritional terms. Moderate ethanol intake from any type of beverage improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether wine, particularly red wine with its abundant content of phenolic acids and polyphenols, confers additional health benefits. Discovering the nutritional properties of wine is a challenging task, which requires that the biological actions and bioavailability of the >200 individual phenolic compounds be documented and interpreted within the societal factors that stratify wine consumption and the myriad effects of alcohol alone. Further challenge arises because the health benefits of wine address the prevention of slowly developing diseases for which validated biomarkers are rare. Thus, although the benefits of the polyphenols from fruits and vegetables are increasingly accepted, consensus on wine is developing more slowly. Scientific research has demonstrated that the molecules present in grapes and in wine alter cellular metabolism and signaling, which is consistent mechanistically with reducing arterial disease. Future research must address specific mechanisms both of alcohol and of polyphenolic action and develop biomarkers of their role in disease prevention in individuals.

Traditional food resources of indigenous peoples are now recognized as containing a variety of environmental contaminants which reach food species through local or long-range transport avenues. In this chapter we review the published reports of contaminants contained in traditional food in northern North America and Europe as organochlorines, heavy metals, and radionuclides. Usually, multiple contaminants are contained in the same food species. Measurement of dietary exposure to these environmental contaminants is reviewed, as are major issues of risk assessment, evaluation, and management. The dilemma faced by indigenous peoples in weighing the multiple nutritional and socioeconomic benefits of traditional food use against risk of contaminants in culturally important food resources is described.

Mammalian iron homeostasis is maintained through the concerted action of sensory and regulatory networks that modulate the expression of proteins of iron metabolism at the transcriptional and/or post-transcriptional levels. Regulation of gene transcription provides critical developmental, cell cycle, and cell-type-specific controls on iron metabolism. Post-transcriptional control through the action of iron regulatory protein 1 (IRP1) and IRP2 coordinate the use of messenger RNA-encoding proteins that are involved in the uptake, storage, and use of iron in all cells of the body. IRPs may also provide a link between iron availability and cellular citrate use. Multiple factors, including iron, nitric oxide, oxidative stress, phosphorylation, and hypoxia/reoxygenation, influence IRP function. Recent evidence indicates that there is diversity in the function of the IRP system with respect to the response of specific IRPs to the same effector, as well as the selectivity with which IRPs modulate the use of specific messenger RNA.

The microsomal triglyceride transfer protein (MTP) is a dimeric lipid transfer protein consisting of protein disulfide isomerase and a unique 97-kDa subunit. In vitro, MTP accelerates the transport of triglyceride, cholesteryl ester, and phospholipid between membranes. It was recently demonstrated that abetalipoproteinemia, a hereditary disease characterized as an inability to produce chylomicrons and very low-density lipoproteins in the intestine and liver, respectively, results from mutations in the gene encoding the 97-kDa subunit of the microsomal triglyceride transfer protein. Downstream effects resulting from this defect include malnutrition, very low plasma cholesterol and triglyceride levels, altered lipid and protein compositions of membranes and lipoprotein particles, and vitamin deficiencies. Unless treated, abetalipoproteinemic subjects develop gastrointestinal, neurological, ophthalmological, and hematological abnormalities.

Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.