PMC

RT-PCR indicated upregulation of hypothalamic Crfr2 (c) and a non-significant 5-fold upregulation of Pomc (a) in periadolescent fructose-fed animals without an effect on Crfr1 (b). In animals fed fructose during adulthood only, there was a non-significant 5-fold upregulation of Pomc (d) but no effect was observed on either Crfr1 (e) or Crfr2 (f).

a. Plasma corticosterone was analyzed and demonstrated significant increases in basal corticosterone in the periadolescent fructose-fed cohort without differences in the forced swim test. b. Rats fed the high-fructose diet during adulthood only did not differ from chow-fed animals in plasma corticosterone. Data shown are mean ± SEM; different letters indicate significant effects in post-hoc testing with p < 0.05. C=Chow, F=Fructose

a. Heatmap of log₂ transformed expression values (FPKM) of the 966 differently expressed transcripts between the two diet conditions (Chow: n=7; Fructose: n=6) in the periadolescent cohort. Zero roughly corresponds to mean expression level. b. Components of the POMC processing pathway and CRF signaling are combined to show altered genes in these pathways. Hues of the boxes indicate relative transcript expression (log₂(FPKM)) in the fructose-fed animals. Differentially expressed genes that pass multiple testing corrections are denoted by an asterisk. C=Chow, F=Fructose

a. Rats fed a high-fructose diet during periadolescence had increased caloric efficiency relative to chow-fed rats. b. Periadolescent fructose-fed rats had significantly higher fasting blood glucose relative to chow-fed rats beginning within 20 days on the diet. c, d. Both epididymal and retroperitoneal fat mass were increased in the periadolescent fructose-fed rats relative to their chow-fed controls. e, f. In rats fed the high-fructose diet during adulthood only, neither caloric efficiency nor blood glucose significantly differed from chow-fed rats. Data shown are mean ± SEM; asterisk indicates an effect of diet in the t-test and a hash tag indicates a significant post-hoc effect between diets at the same time point with p < 0.05.

a. Periadolescent fructose-fed rats showed increased activity in the open field. b. Fructose-feeding during periadolescence reduced central tendency, while adolescent stress increased central tendency. c. Periadolescent fructose-fed rats reduced time spent in the open arms of the elevated plus maze. d, e, f. Periadolescent fructose-fed rats spent significantly less time struggling, had reduced latency to float, and spent more time immobile in the forced swim test than standard chow fed rats. g, h, i. Rats fed the high-fructose diet in adulthood only did not differ from chow controls in open field or elevated plus maze behavior. j, k, l. Rats that consumed the fructose diet in adulthood only did not change in either struggling (p>0.05) or immobility (p>0.05) in the forced swim. However, there was a numeric reduction in latency to float in the adult fructose-fed rats (t₁₄=2.094 p=0.0549). Data shown are mean ± SEM; asterisk indicates a main effect of diet while letters indicate significant post-hoc effects with p < 0.05. NS=Non-stressed; S=Stressed

a. The percent of weight gained during the mid-adolescent stressor (PND37-49) was reduced in the stress cohorts (p<0.05) and fructose-fed animals gained more weight during this period (p<0.05). b. The fructose diet also significantly increased fasting glucose during mid-adolescence (p<0.05) irrespective of stress history. c. Glucose administration in the glucose tolerance test raised blood glucose in both chow and fructose stress & non-stress groups (p<0.05) as expected. However, fructose diet exacerbated this effect and fructose-fed rats had significantly higher blood glucose in the glucose challenge than the standard chow fed rats (p<0.05). d. Only a main effect of glucose administration (p < 0.05) was observed in analysis of plasma insulin; neither fructose nor stress, nor an interaction of either with the other or with glucose altered plasma insulin. Data shown are mean ± SEM; different letters indicate significant differences (p < 0.05) as assessed by post-hoc testing. NS=Non-stressed; S=Stressed; C=Saline-injected control; G=Glucose-injected