There are multiple hypotheses for the causes of the obesity epidemic. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine some the unique metabolic changes that occur with initial exposure to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24 h, after which blood and tissues were collected. Fructose access (as opposed to other sugars investigated) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake.

Stimulated by retinoic acid homolog 6 (STRA6) is a transmembrane receptor specific for retinol‐binding protein 4 (RBP4) that mediates uptake of retinol bound to RBP4 (HoloRBP4). Retinoic acid derivatives of retinol have well‐documented anti‐proliferative actions that are mediated by retinoic acid and retinoid X receptors (RAR and RXR, respectively). Thus, it has long been assumed that the effects of circulating retinol on the regulation of apoptosis are dependent on cellular uptake of retinol and activation to retinoic acid. An additional role of STRA6 has recently been identified in vivo and in cultured hepatocytes and renal proximal tubule cells. Upon binding to holoRBP4, STRA6 has been shown to activate a cascade that led to STAT5‐mediated gene regulation. We have detected and induced STRA6 with all‐trans‐retinoic acid (RA) in PC‐3 prostate cancer cells. In this study, we found that PC‐3 cells were growth inhibited following treatment with holoRBP4 whereas 1 μmol/L RA treatment had no effect. Furthermore, we observed that holoRBP4 treatment reduced mRNA and protein abundance of cell cycle progression proteins (CD1, CDK2, and CDK4), which have been identified as a downstream target of STAT5. Collectively, these results indicate that anti‐proliferative actions of retinol may be produced via a signal transduction mechanism, which appear to occur independently of RA‐mediated gene regulation.Grant Funding Source: National Institutes of Health

Identification of an internal control gene for normalization is required for qRT‐PCR experiments. Vandersompele et al (2002) have demonstrated the need for housekeeper genes that are unaffected by experimental treatments. Several investigators have selected β‐actin as the preferred housekeeper in examining the effects of sugars on hypothalamic appetite regulatory genes. We set out to determine if access to different sugar solutions could alter hypothalamic gene expression in rats. Presented are three sets of observations related to the selection of a housekeeper. First β‐actin varied across treatments, making it a poor choice. Second, a poorly selected housekeeper can result in reporting of false conclusions. When fold change was calculated using β‐actin, differences in AGRP were observed among treatment groups. However, when analyzed with RPLP as housekeeper no differences were observed. Third, sometimes using a poor housekeeper does not lead to false conclusions. Differences in some genes were significant independent of the housekeeper. Here we demonstrate that housekeeper selection can impact conclusions. Supported in part by a grant from the Maryland Agricultural Experiment Station.

Fructose consumption can influence several systems that regulate food intake in ways that differ from those promoted by glucose intake. In particular fructose access uniquely leads to changes in several genes in the hypothalamus that have been linked to appetite control.Rats were given access to food, water and one of several sugar solutions for 24 h, after which blood and tissues were collected. Separate 16% (w/v) solutions of glucose, sucrose, high fructose corn syrup, and fructose were tested. Despite differences in their sweetness, palatability and metabolic effects, all of the solutions were consumed in similar amounts. All groups given access to sugar consumed more calories than did controls. Overnight fructose access (as opposed to other sugars) led to a doubling of circulating triglycerides. Hypothalamic dopamine receptors 1a and 2 and Neuropeptide Y messages were upregulated in only the fructose fed rats. Hypothalamic Galanin, Brs3, AGRP, INSR, Gh1, Trhr, Atrn, NMB, TNF and Thrb were downregulated only in the fructose group. Unlike fructose, preliminary comparisons of sucrose and HFCS to glucose have failed to reveal any differences in these end points.(Supported by a grant from the Maryland Agricultural Experiment Station)