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Abstract Mammals have evolved complex regulatory systems that enable them to maintain energy homeostasis despite constant environmental challenges that limit the availability of energy inputs and their composition. Biological control relies upon intricate systems composed of multiple organs and specialized cell types that regulate energy up-take, storage, and expenditure. Because these systems simultaneously perform diverse functions and are highly integrated, they are extremely difficult to understand in terms of their individual component contributions to energy homeostasis. In order to provide improved treatments and clinical options, it is important to identify the principle genetic and molecular components, as well as the systemic features of regulation. To begin, many of these features can be discovered by integrating experimental technologies with advanced methods of analysis. This review focuses on the analysis of transcriptional data derived from microarrays and how it can complement other experimental techniques to study energy homeostasis.

Abstract Background Obesity is associated with insulin resistance that can often be improved by caloric restriction and weight reduction. Although many physiological changes accompanying insulin resistance and its treatment have been characterized, the genetic mechanisms linking obesity to insulin resistance are largely unknown. We used DNA microarrys and RT-PCR to investigate significant changes in hepatic gene transcription in insulin resistant, diet-induced obese (DIO)-C57/BL/6J mice and DIO-C57/BL/6J mice fasted for 48 hours, whose weights returned to baseline levels during these conditions. Results Transcriptional profiling of hepatic mRNA revealed over 1900 genes that were significantly perturbed between control, DIO, and fasting/weight reduced DIO mice. From this set, our bioinformatics analysis identified 41 genes that rigorously discriminate these groups of mice. These genes are associated with molecular pathways involved in signal transduction, and protein metabolism and secretion. Of particular interest are genes that participate in pathways responsible for modulating insulin sensitivity. DIO altered expression of genes in directions that would be anticipated to antagonize insulin sensitivity, while fasting/ weight reduction partially or completely normalized their levels. Among these discriminatory genes, Sh3kbp1 and RGS3, may have special significance. Sh3kbp1, an endogenous inhibitor of PI-3-kinase, was upregulated by high-fat feeding, but normalized to control levels by fasting/weight reduction. Because insulin signaling occurs partially through PI-3-kinase, increased expression of Sh3kbp1 by DIO mice may contribute to hepatic insulin resistance via inhibition of PI-3-kinase. RGS3, a suppressor of G-protein coupled receptor generation of cAMP, was repressed by high-fat feeding, but partially normalized by fasting/weight reduction. Decreased expression of RGS3 may augment levels of cAMP and thereby contribute to increased, cAMP-induced, hepatic glucose output via phosphoenolpyruvate carboxykinase (PCK1), whose mRNA levels were also elevated. Conclusion These findings demonstrate that hepatocytes respond to DIO and weight reduction by controlling gene transcription in a variety of important molecular pathways. Future studies that characterize the physiological significance of the identified genes in modulating energy homeostasis could provide a better understanding of the mechanisms linking DIO with insulin resistance.

A 41-d feeding trial was conducted to determine the efficacy of a corn-expressed phytase (GZ; GraINzyme, Agrivida Inc. Woburn, MA) on the live performance, bone characteristics, and P digestibility of nursery pigs fed a reduced P diet. Weaned piglets (21 ± 3 d; n = 324) were acclimated on a common diet for 7 d (phase 1) before randomization into 54 single-sex pens (5 gilt and 4 barrow pens per treatment) containing 6 pigs (6.6 ± 1.2 kg) per pen. Six treatments were fed: positive control (PC ; 0.4% or 0.32% aP for phase 2 or 3 and 4, respectively), negative control (NC ; 0.15% reduction in aP), and 500, 1,000, 2,000, or 4,000 FTU per kg phytase from GZ added to NC in a 3-phase feeding program. Pigs were weighed on day 1, 14, 28, and 41, and feed disappearance recorded per phase. Apparent total tract digestibility (ATTD) of P was determined by feeding chromic oxide marker (day 28 to 35) and collecting fecal samples on day 35. On day 41, 4 pigs per pen were euthanized and metacarpal bones were collected to evaluate bone breaking strength (BBS) and ash. Data were analyzed using PROC GLM of SAS (block, sex, and treatment). Treatment least squares means were separated and linear and quadratic treatment effects evaluated. Other than feed efficiency (G:F) and day 15 to 28 ADFI, the pigs fed PC were superior (P < 0.05) to NC-fed pigs in all other variables. Pigs fed ≥500 FTU per kg phytase had increased (P < 0.05) ADG and ADFI compared to NC pigs and equivalent (P > 0.05) ADG and ADFI as PC pigs from day 0 to 41. Feeding ≥500 FTU per kg phytase resulted in higher (P < 0.05) ATTD of P than both NC and PC pigs and higher (P < 0.05) BBS and bone ash weight than NC. Pigs fed 1,000 or 2,000 FTU per kg phytase had equivalent (P > 0.05) BBS and bone ash weight compared to pigs fed PC diets. Feeding 4,000 FTU per kg phytase resulted in higher (P < 0.05) day 1 to 41 ADG, ATTD of P, and bone ash weight compared to feeding ≤1,000 FTU per kg phytase or PC diets. There were linear (P < 0.05) increases in ADG, ADFI, ATTD of P, BBS, and bone ash characteristics as GZ inclusion increased. In conclusion, ≥500 FTU per kg phytase from GZ improved growth, ATTD of P, BBS, and bone ash when added to a reduced P diet and 4,000 FTU per kg phytase increased growth greater than the PC treatment. [ABSTRACT FROM AUTHOR]