There is little information regarding effects of fasting on feeding behavior and hypothalamic physiology in young Japanese quail. The aim was thus to measure food intake and hypothalamic mRNA in respo Show more
There is little information regarding effects of fasting on feeding behavior and hypothalamic physiology in young Japanese quail. The aim was thus to measure food intake and hypothalamic mRNA in response to fasting and refeeding. Five d-old quail ate little during the dark cycle. Food intake was greatest during the first 2 h of the light cycle. Six day-old quail fasted for 6 h ate the most during the first 15 min of refeeding. In 7 d-old quail, 3 h of fasting up-regulated hypothalamic neuropeptide Y (NPY), NPY receptor sub-type 2 (NPYR2), agouti-related peptide (AgRP), orexin receptor 2 (ORXR2), melanocortin receptors 3 and 4 (MC3R and MC4R, respectively), and neuropeptide S (NPS) and decreased corticotropin-releasing factor receptor sub-type 1 (CRFR1) mRNA. Quail fasted for 3 h and refed for 1 h had greater NPY, AgRP, POMC, and MC3R but less CRFR1 mRNA than fed quail. Quail fasted for 6 h expressed more NPY, NPYR1, NPYR2, and MC3R and less ORXR2, prolactin releasing peptide (PrRP), cocaine- and amphetamine-regulated transcript (CART), and calcitonin (CAL) mRNA than fed quail. Quail fasted for 6 h and refed for 1 h expressed more NPY, NPYR1, NPYR2, AgRP, MC3R, MC4R, and NPS and less galanin, ORXR2, PrRP, CART, and CAL mRNA than fed birds. Hence, fasting induced changes in hypothalamic mRNA, with the largest changes occurring in genes associated with NPY and melanocortin signaling. Most genes remained elevated or downregulated after refeeding, suggesting that there was a time lag for transcription to respond to compensatory feeding. Show less
By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to co Show more
By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP is a potential therapeutic target, we decreased hepatic expression of ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley rats fed either a high-fructose or high-fat diet. ChREBP ASO treatment decreased plasma triglyceride concentrations compared with control ASO treatment in both diet groups. The reduction was more pronounced in the fructose-fed group and attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a decrease in the rate of hepatic triglyceride secretion. This was associated with an increase in insulin-stimulated peripheral glucose uptake, as assessed by the hyperinsulinemic-euglycemic clamp. In contrast, ChREBP ASO did not alter hepatic lipid content or hepatic insulin sensitivity. Interestingly, fructose-fed rats treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and aspartate aminotransferase concentrations. This was associated with decreased expression of fructose aldolase and fructokinase, reminiscent of inherited disorders of fructose metabolism. In summary, these studies suggest that targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without the improvements in hepatic steatosis and hepatic insulin responsiveness. Show less