Energy density and macronutrient composition determine flavor preference conditioned by intragastric infusions of mixed diets.
ABSTRACT In prior studies rats preferred a flavor (CS+HF) paired with intragastric (IG) infusions of a high-fat diet to a flavor (CS+HC) paired with a high-carbohydrate diet, yet just the opposite preference was observed with pure-nutrient infusions. The present study tested the hypothesis that variations in nutrient density as well as composition influence flavor learning. Animals were trained (22 h/day) with IG infusion of milk-based high-fat and high-carbohydrate liquid diets paired with intakes of flavored, noncaloric CS+ solutions. A third flavor, the CS-, was paired with water infusion. Standard chow was available ad libitum. The rats preferred both CS+ flavors to the CS-, whether the infused diets were dense (HF and HC, 2.1 kcal/ml) or dilute (hf and hc, 0.5 kcal/ml), indicating that all diet infusions were reinforcing. They consumed the CS+hc and CS+hf equally in training, and preferred the CS+hc, showing that at low-energy density carbohydrate was more reinforcing than fat. In contrast, CS+HF intake exceeded that of CS+HC in training, and the rats preferred the CS+HF to the CS+HC. In further tests the rats preferred the CS+HF to the CS+hc, the CS+HF to the CS+hf, and the CS+HC to the CS+hc; i.e., when the diets differed in energy density the flavors associated with the more concentrated infusions were preferred. In the absence of influence by flavor cues from the nutrients themselves, rats' preferences for flavors associated with diets high in fat or carbohydrate are dependent on energy density. The differential satiating effects of fat and carbohydrate may contribute to these density-dependent preferences.
Article: Intracisternal administration of transforming growth factor-beta evokes fever through the induction of cyclooxygenase-2 in brain endothelial cells.[show abstract] [hide abstract]
ABSTRACT: Transforming growth factor-beta (TGF-beta), a pleiotropic cytokine, regulates cell proliferation, differentiation, and apoptosis, and plays a key role in development and tissue homeostasis. TGF-beta functions as an anti-inflammatory cytokine because it suppresses microglia and B-lymphocyte functions, as well as the production of proinflammatory cytokines. However, we previously demonstrated that the intracisternal administration of TGF-beta induces fever like that produced by proinflammatory cytokines. In this study, we investigated the mechanism of TGF-beta-induced fever. The intracisternal administration of TGF-beta increased body temperature in a dose-dependent manner. Pretreatment with cyclooxygenase-2 (COX-2)-selective inhibitor significantly suppressed TGF-beta-induced fever. COX-2 is known as one of the rate-limiting enzymes of the PGE(2) synthesis pathway, suggesting that fever induced by TGF-beta is COX-2 and PGE(2) dependent. TGF-beta increased PGE(2) levels in cerebrospinal fluid and increased the expression of COX-2 in the brain. Double immunostaining of COX-2 and von Willebrand factor (vWF, an endothelial cell marker) revealed that COX-2-expressing cells were mainly endothelial cells. Although not all COX-2-immunoreactive cells express TGF-beta receptor, some COX-2-immunoreactive cells express activin receptor-like kinase-1 (ALK-1, an endothelial cell-specific TGF-beta receptor), suggesting that TGF-beta directly or indirectly acts on endothelial cells to induce COX-2 expression. These findings suggest a novel function of TGF-beta as a proinflammatory cytokine in the central nervous system.AJP Regulatory Integrative and Comparative Physiology 02/2008; 294(1):R266-75. · 3.34 Impact Factor