Rats Acquire Stronger Preference for Flavors Consumed Towards the End of a High-fat Meal

Rats learn to prefer flavors associated with postingestive effects of nutrients. The physiological signals underlying this postingestive reward are unknown. We have previously shown that rats readily learn to prefer a flavor that was consumed early in a multi-flavored meal when glucose is infused intragastrically (IG), suggesting rapid postingestive reward onset. The present experiments investigate the timing of postingestive fat reward, by providing distinctive flavors in the first and second halves of meals accompanied by IG fat infusion. Learning stronger preference for the earlier or later flavor would indicate when the rewarding postingestive effects are sensed. Rats consumed sweetened, calorically-dilute flavored solutions accompanied by IG high-fat infusion (+ sessions) or water (− sessions). Each session included an “Early” flavor for 8 min followed by a “Late” flavor for 8 min. Learned preferences were then assessed in two-bottle tests (no IG infusion) between Early(+) vs. Early(−), Late(+) vs. Late(−), Early(+) vs. Late(+), and Early(−) vs. Late(−). Rats only preferred Late(+), not Early(+), relative to their respective (−) flavors. In a second experiment rats trained with a higher fat concentration learned to prefer Early(+) but more strongly preferred Late(+). Learned preferences were evident when rats were tested deprived or recently satiated. Unlike with glucose, ingested fat appears to produce a slower-onset rewarding signal, detected later in a meal or after its termination, becoming more strongly associated with flavors towards the end of the meal. This potentially contributes to enhanced liking for dessert foods, which persists even when satiated.

Rats Acquire Stronger Preference for Flavors Consumed Towards the End of a High-fat Meal

Rats learn to prefer flavors associated with postingestive effects of nutrients. The physiological signals underlying this postingestive reward are unknown. We have previously shown that rats readily learn to prefer a flavor that was consumed early in a multi-flavored meal when glucose is infused intragastrically (IG), suggesting rapid postingestive reward onset. The present experiments investigate the timing of postingestive fat reward, by providing distinctive flavors in the first and second halves of meals accompanied by IG fat infusion. Learning stronger preference for the earlier or later flavor would indicate when the rewarding postingestive effects are sensed. Rats consumed sweetened, calorically-dilute flavored solutions accompanied by IG high-fat infusion (+ sessions) or water (- sessions). Each session included an "Early" flavor for 8min followed by a "Late" flavor for 8min. Learned preferences were then assessed in two-bottle tests (no IG infusion) between Early(+) vs. Early(-), Late(+) vs. Late(-), Early(+) vs. Late(+), and Early(-) vs. Late(-). Rats only preferred Late(+), not Early(+), relative to their respective (-) flavors. In a second experiment rats trained with a higher fat concentration learned to prefer Early(+) but more strongly preferred Late(+). Learned preferences were evident when rats were tested deprived or recently satiated. Unlike with glucose, ingested fat appears to produce a slower-onset rewarding signal, detected later in a meal or after its termination, becoming more strongly associated with flavors towards the end of the meal. This potentially contributes to enhanced liking for dessert foods, which persists even when satiated.

A new model of interactive effects of alcohol and high-fat diet on hepatic fibrosis

Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are the most frequent conditions leading to elevated liver enzymes and liver cirrhosis, respectively, in the Western world. However, despite strong epidemiological evidence for combined effects on the progression of liver injury, the mutual interaction of the pathophysiological mechanisms is incompletely understood. The aim of this study was to establish and analyze an experimental murine model, where we combined chronic alcohol administration with a NASH-inducing high-fat (HF) diet.

Soluble CD163 is not increased in visceral fat and steatotic liver and is even suppressed by free fatty acids in vitro

Visceral fat differs from subcutaneous fat by higher local inflammation and increased release of IL-6 and free fatty acids (FFA) which contribute to hepatic steatosis. IL-6 has been shown to upregulate the monocyte/macrophage specific receptor CD163 whose soluble form, sCD163, is increased in inflammatory diseases. Here, it was analyzed whether CD163 and sCD163 are differentially expressed in the human fat depots and fatty liver. CD163 mRNA and protein were similarly expressed in paired samples of human visceral and subcutaneous fat, and comparable levels in portal venous and systemic venous blood of liver-healthy controls indicate that release of sCD163 from visceral adipose tissue was not increased. CD163 was also similarly expressed in steatotic liver when compared to non-steatotic tissues and sCD163 was almost equal in the respective sera. Concentrations of sCD163 were not affected when passing the liver excluding substantial hepatic removal/release of this protein. A high concentration of IL-6 upregulated CD163 protein while physiological doses had no effect. However, sCD163 was not increased by any of the IL-6 doses tested. FFA even modestly decreased CD163 and sCD163. The anti-inflammatory mediators fenofibrate, pioglitazone, and eicosapentaenoic acid (EPA) did not influence sCD163 levels while CD163 was reduced by EPA. These data suggest that in humans neither visceral fat nor fatty liver are major sources of sCD163.

Effects of Aerobic Versus Resistance Exercise Without Caloric Restriction on Abdominal Fat, Intrahepatic Lipid, and Insulin Sensitivity in Obese Adolescent Boys: A Randomized, Controlled Trial

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and secretion in youth. Forty-five obese adolescent boys were randomly assigned to one of three 3-month interventions: AE, RE, or a nonexercising control. Abdominal fat was assessed by magnetic resonance imaging, and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy. Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp. Both AE and RE prevented the significant weight gain that was observed in controls. Compared with controls, significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups. Compared with controls, a significant improvement in insulin sensitivity (27%) was observed in the RE group. Collapsed across groups, changes in visceral fat were associated with changes in intrahepatic lipid (r = 0.72) and insulin sensitivity (r = -0.47). Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys. RE but not AE is also associated with significant improvements in insulin sensitivity.