Page 47 - Small Animal Clinical Nutrition 5th Edition

Nutritional Genomics 47

dictable metabolic and genetic adaptations that occurred in rat Box 4-1. The Value of Sequencing the
VetBooks.ir pups during the dietary intervention continued to be expressed Canine and Feline Genomes.
into adulthood. As adults, these rats demonstrated chronic
Because of the cost of sequencing mammalian genomes to
hyperinsulinemia and adult onset obesity (Srinivasan et al,
2003; Swanson, 2006). completion (approximately $50 million U.S.), these projects
There are also nutrigenomic studies in dogs associating spe- have been restricted to a few species considered to be of
cific nutrients to obesity and insulin sensitivity. Dogs fed a food greatest value to biomedical research. Knowledge of human
designed to induce obesity and insulin resistance had a decrease genome function in health and disease will benefit from com-
in the expression of uncoupling protein 1 (UCP1) and peroxi- parison of its structure with genomes of certain other species.
The dog is a particularly good example because of its some-
some proliferator-activated receptor gamma (PPARγ) in their what unique population structure.The physical and behavioral
adipose tissue compared to non-obese, insulin-sensitive dogs characteristics of approximately 300 breeds are maintained
(Leray et al, 2004). PPARγ plays a role in adipocyte differenti- by restricting gene flow between breeds. Many modern
ation, lipid storage and glucose homeostasis and induces the breeds have been inbred for desired characteristics. This has
expression of many genes including UCP1, which plays a key led to a species with enormous phenotypic diversity but with
role in thermogenesis. significant homogenization of the gene pool within breeds.
Nutrigenomic studies in dogs have also shown that obesi- Many of the approximately 450 known genetic disorders in
ty-related hypertension causes marked changes in gene dogs resemble human conditions, and their causes may be
expression in the right atrium and left ventricle. These more traceable in large dog pedigrees than in small, outbred
changes were thought to contribute to early changes in heart human families. The combination of genetic homogeneity and
function, hypertrophy and remodeling (Philip-Couderc et al, phenotypic diversity also provides an opportunity to under-
stand the genetic basis of many complex developmental
2003). Other studies focusing on gene expression in the left processes in mammals. Thus, to a large part, funding of the
ventricles of dogs fed normal or high-fat foods using canine sequencing of the canine genome and the genome of certain
cDNA arrays identified 63 differentially expressed genes other mammalian species is based on their value in further
involved in metabolism, cell signaling, tissue remodeling, understanding human health and disease.
insulin regulation, cell proliferation and protein synthesis.
The results of this study further indicated that the pattern of
co-regulated genes depended on the length of time that the The Bibliography for Box 4-1 can be found at
www.markmorris.org .
high-fat food was fed. These findings suggested that hyper-
tension resulting from obesity induced by high dietary fat was
associated with continuous cardiac transcriptome adaptation
despite stability in both body weight and blood pressure
(Philip-Couderc et al, 2004).
Proteomic studies determined that supplementing rat food
with genistein, a major isoflavone from soy, increased the THE CANINE AND FELINE GENOMES:
expression of mammary gland GTP cyclohydrolase-I, a key CURRENT STATUS
protein related to nitrogen oxide synthesis. There was a result-
ant reduction in cell proliferation and susceptibility to cancer The primary reason for funding the sequencing of the canine and
(Rowell et al, 2005). Another study showed that inadequate feline genomes was to provide a basis for future comparative work
provision of dietary vitamin B 12 induced profound changes in in human biology including development, aging, cancer, herita-
the cerebral spinal fluid proteome in rats, linking vitamin B 12 ble diseases and immune diseases. Dogs and cats have numerous
with neurologic health (Gianazza et al, 2003). heritable diseases, many of which are homologous to human
An example of a potential indirect effect via metabolites is inborn errors. Furthermore, the susceptibility of cats to viruses
that of dietary fiber on transcription. One study reported that cause immunodeficiencies and neoplasias (feline immunode-
increased adipocyte leptin expression in cell cultures treated ficiency virus and feline leukemia virus, respectively) make them
with physiologic amounts of short-chain fatty acids (Xiong et important models for human AIDS and leukemia research.
al, 2004). Short-chain fatty acids from colonic microbial fer-
mentation of dietary fibers may help protect against overeating Canine Genome
and obesity by decreasing appetite through leptin expression A sequenced genome could provide the basis for valuable infor-
(Swanson, 2006). mation to determine the molecular differences between health
Through traditional methods, key nutritional factors (essen- and disease in dogs. The dog was the first non-rodent mam-
tial nutrients and bioactive food components) have long been malian animal chosen for genome sequencing by the National
established as potential modulators of health and disease Institutes of Health (Box 4-1) (Swanson, 2006). The sequence
(Watson, 1998; Dove, 2001; DeBoer, 2004). Understanding was derived for a male standard poodle; investigators estimated
the ways in which foods and their components affect gene the genome to contain approximately 2.4 billion bases (Gb),
expression will further enhance use of key nutritional factors to which is about the same as the mouse genome but smaller than
modulate health and disease. the human genome (approximately 2.9 Gb). With private and