Influence of maternal macronutritional diet on the developme(n)t of obesity, glycometabolic disorders, and anxiety-/depression- like behaviour of offspring

The maternal diet during gestation may have a significant impact on offspring development and their health later in life. However, it is unknown to what degree the different macronutrients ingested during pregnancy will affect body weight, metabolism and behaviours of the offspring. The aim of this study is therefore to investigate the effects of maternal macronutritional diet during the gestational period on the development of obesity, the glycometabolism, and anxiety- and depression-like behaviours in mice offspring. Female C57BL/6J mice were fed Lab Chow (control) or one of 3 fabricated diets high in monosodium glutamate (MSG), fat (HF) or carbohydrate (HS) 2 weeks prior to and during mating, throughout gestation, but not during lactation. Body weight and food intake of male mice offspring were recorded for 23 weeks to determine when offspring became obese. A glucose tolerance test (GTT) was conducted on mice at weeks 13, 19 and 22 to determine when obesity started to affect glucose metabolism. Behavioural tests (open field, elevated maze, novelty suppressed feeding and forced swimming test) were conducted on weeks 5, 13 and 23 , aiming to determine the possible point at which obesity commenced to effect anxiety/depression-like behaviours. Two weeks after the mothers were on a HF, HS or MSG diet they were heavier than mothers fed a LC diet. Also, the mothers fed a HS diet had a heavier litter than the mothers fed a HF or MSG diet. Offspring during breast feeding (at age 2 and 3 weeks) from mothers fed HF, HS or MSG were heavier than offspring from mothers fed a LC diet. After weaning, offspring fed LC from mothers fed LC had a significantly lower food intake and BW than offspring from mothers fed a HF, HS, or MSG diet. Offspring fed an Ob diet from a mother fed LC had a significantly lower food intake and BW than offspring from a mother fed HF, HS or MSG. In this regard, omenta fat was lower in mice fed LC from mothers fed LC than in mice fed LC or Ob diet from mothers fed HF, HS or MSG. The results of the GTT showed that different maternal macronutritional (HF, HS, MSG and LC as control) diets affect the blood glucose levels in offspring differently. Mice fed an Ob diet showed higher glucose levels than mice fed LC diet. Behaviour tests at different offspring ages indicated the development of some anxiety/ depression like behaviours. In the elevated maze test mice in the LCm/LCo group showed more entries and more full body entries into the OA than mice from all other groups (HFm/LCo, HSm/LCo, MSGm/LCo, LCm/Obo, HFm/Obo, HSm/Obo and MSGm/Obo). Mice in LCm/LCo group therefore showed less anxiety like behaviour than mice from all others groups. During the open field test rearing frequency was higher in mice in the groups LCm/LCo and LCm/Obo than in mice in all other groups (HFm/LCo, HSm/LCo, MSGm/LCo, HFm/Obo, HSm/Obo and MSGm/Obo). A high frequency of this behaviour indicates increased locomotor and exploratory activities, and a lower level of anxiety. In addition, the forced swimming test in all 3 age groups (5, 13 and 23 weeks) showed that the maternal HS, HF and MGS diets increased immobility time in mice from the HFm/LCo, HSm/LCo and MSGm/LCo group. The increased immobility time in the FST indicated levels of depression-like behaviour in mice. This study produced mice offspring which were able to gain body weight and develop obesity earlier than the control group because their mothers were programmed by a macronutritional diet (HF, HS, MSG) during the gestation period. Later in life, the mice offspring might have developed glycometabolic disorders, possibly followed by the development of anxiety- and depression-like symptoms. These findings have important implications in advising future mothers to be of the importance of gestational diet for the health of their children