Dissertation committee:
Εμμανουήλ Πικουλής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δέσποινα Περρέα, Ομότιμη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ανδρέας Λάζαρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αφροδίτη Νόννη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Χαρίκλεια Γακιοπούλου, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ειρήνη Θυμαρά, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Caffeine (1,3,7-trimethylxanthine) is a food component consumed worldwide on a daily basis mainly due to its special psychoactive properties. It is present in various liquid foods, including coffee, tea, soft drinks, energy drinks, but also in solid foods such as chocolate and it is considered one of the most widely consumed components in human’s diet.
The continuing increased trend in caffeine consumption, as well as the fact that it is completely metabolized by the human body and particularly to a greater extent by the enzyme CYP1A2 which is located in the liver, have raised great concern about its effects on human health among the scientific community. Several studies have been conducted in order to investigate the potential effects of caffeine intake on the development, deterioration or improvement of various metabolic diseases, including metabolic syndrome, which is characterized by a cluster of metabolic complications, including abdominal obesity and insulin resistance.
In addition, it has been found that caffeine consumption during pregnancy may lead to adverse effects on pregnancy and a disturbed metabolic profile in the offspring during adulthood. Moreover, the fact that during pregnancy caffeine reaches fetus circulation by freely penetrating the placenta and has a half-life of up to 100 hours further reinforces the concerns of scientists. Based on the recommendations of EFSA and IOM, the maximum consumption should be considered as 2 cups of coffee per day, an amount equivalent to approximately 200 mg of caffeine. However, studies show that even this recommendation may be a high and dangerous limit with possible negative effects on both progress of pregnancy and health of the newborn.
The aim of the present thesis was to investigate the effects of intrauterine caffeine exposure on the metabolic profile of male Sprague Dawley rats after consumption of a high-fructose solution.
Five-month-old female Sprague Dawley rats were matched with males of a respective age. Males were housed with the females for four days to ensure completion of one estrous cycle and were consequently removed. Initiating on entry of the males and up to the day of birth, pregnant rats were administered ad libitum tap water (group A of mothers, control, n=10) or caffeine-enriched water (group B of mothers, n=10), in a concentration estimated to equal a daily caffeine uptake of 20 mg/kg of body weight. The main sample of the study was 40 male offspring, 20 from each group, which were divided into 4 groups. Upon adulthood (10 weeks old), the selected offspring were assigned to four different subgroups: A1 (n=10), males born of control mothers; A2 (n=10), males born of control mothers, receiving a high-fructose water solution (200 g/l) on a daily basis instead of tap water; B1 (n=10), males prenatally exposed to caffeine; B2 (n=10), males prenatally exposed to caffeine which received a high-fructose water solution (200 g/l) daily instead of tap water.
Blood samples of male offspring were collected upon adulthood (T1), one month later (T2), and two months (T3). Measurements included body weight, blood pressure and biochemical indices (glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol). Insulin resistance was also measured by the OGTT method, while histopathological analysis of renal and hepatic tissue was performed.
The results showed a statistically significant increase (p<0.05) in triglyceride levels in group B2 compared to the other experimental groups. Moreover, prenatal exposure to caffeine led to a significant increase (p<0.05) in both systolic and diastolic blood pressure compared to control groups. In addition, a significantly (p<0.05) lower birth weight was found in the offspring of mothers exposed to caffeine compared to the other groups. Regarding the histopathologic examination, the offspring of mothers exposed to caffeine either in drinking water group (p=0.033) or in the fructose group (p=0.003) had statistically significant higher number of cases with oedema in renal tissue compared to the offspring of mothers not exposed to caffeine. Finally, no differences were observed in renal or hepatic tissue swelling between groups.
In conclusion, this study is the first study to examine the effects of prenatal caffeine exposure (PCE) on a MetS model induced by a high-fructose diet in adulthood. The results of the present study clearly indicated the phenotypic effects of PCE on MetS development in adulthood. Of course, as in all experimental studies, the results should be viewed from a translational point of view and not transmitted directly to humans.
Keywords:
Caffeine, Gestation, Offspring, Rats, Lipids, Blood pressure
