Dietary and physical training effects on the F0 generation

The results reported in the present study confirm previous findings, indicating that animals exposed to a HS/HF diet tend to display weight gain and metabolic changes when compared to those on a standard diet. This confirms dietary efficiency, as it is rich in lipids and/or carbohydrates.^{Reference Stanford, Lee, Getchell, So, Hirshman and Goodyear12,Reference Flores, Fernandes and Ropelle19–Reference Sheldon, Nicole Blaize and Fletcher21} However, to date, no reports are available in the literature concerning the effects of the interaction between the sucrose- and lipid-rich diet applied in this study and physical treadmill training before pregnancy.

Our study corroborates literature data, proving that exercise displays an important translational implication for maternal obesity. Despite some the fact that some authors have applied voluntary exercise, in order to control exercise speed and frequency, an established protocol was used, and the results confirm that the treadmill running training protocol was effective, since the work calculation results indicate improvements in the physical performance of trained animals, even when consuming an HS/HF diet. Physical training prior to pregnancy resulted in health benefits, such as decreased body weight and lipid and glycemic profile improvements in the DHExe group compared to the DHSed group. These results are aligned with studies that indicate that rats subjected to physical training when on a fat-rich diet present lower body weight gain^{Reference Levin and Dunn-Meynell22} and glucose, triglyceride and total cholesterol level decreases.^{Reference Gomes, Marques and Torrezan20,Reference Raipuria, Bahari and Morris23,Reference Vega, Reyes-Castro, Bautista, Larrea, Nathanielsz and Zambrano24}

The importance of physical training on body weight maintenance and aerobic metabolism improvements has been shown^{Reference Dishman, Berthoud and Booth25} and is associated with positive physiological adaptations. These promote increased metabolic rate and stimulate the use of energetic substrates, such as glucose and fatty acids, which lead to direct effects mainly on serum glucose and lipid levels.^{Reference Slentz, Houmard and Kraus26,Reference Slentz, Bateman and Willis27} This, in turn, leads to improvements in glycemic and lipid profiles. Therefore, physical training can prevent and attenuate comorbidities, restoring normoglycemia and insulin sensitivity, as well as dyslipidemia, optimizing metabolic profile changes.^{Reference Slentz, Bateman and Willis27–Reference Andreazzi, Grassiolli and Marangon29} Regarding maternal generation, the HS/HF diet resulted in a slight glucose intolerance among sedentary groups and, corroborating literature assessments, decreased glucose uptake and subsequent cellular oxidation, along with increased gluconeogenesis via hepatic pathways, may result in hyperglycemia.^{Reference Slentz, Houmard and Kraus26,Reference Vanheest and Rodgers30} However, no significant changes among the exercised groups were observed. This may be due to the removal of the exercise stimulus during pregnancy and lactation in the CExe and DHExe groups.^{Reference Vanheest and Rodgers30}

Consistent with findings of other studies applying diet and exercise prior or during pregnancy, it may be better to focus on interventions that improve metabolic fitness rather than only controlling maternal body weight, important in light of recent human studies that have indicated the possibility of modulating behavior in obese pregnant women as a potential long-term effect of these interventions in offspring.^{Reference Alfaradhi, Kusinski and Fernandez-Twinn31} These effects were observed in the present study, where exercise prior to pregnancy contributed to the improvement of metabolic parameters in the mother and/or the offspring.

According to literature, some mechanistic pathways may explain the beneficial effects of maternal exercise in obese mother glucose and triglyceride concentrations. In this case, maternal exercise effect may be linked to reduced circulating blood glucose due to increased glucose uptake rates in skeletal muscles and other peripheral tissues. In addition, some of the metabolic effects of maternal exercise during pregnancy in adult offspring, such as improvement of glucose tolerance, may be associated with enhanced insulin sensitivity, as physical activity is well known to improve both glucose tolerance and insulin sensitivity.^{Reference Raipuria, Bahari and Morris23,Reference Vega, Reyes-Castro and Bautista32–Reference Fernandez-Twinn, Gascoin and Musial34}

Effects on descendants

Concerning the transgenerational metabolic programming model, the results of the present study demonstrate the model efficacy in inducing changes to offspring in future generations. This was more evident in males, especially those belonging to the F2 generation, which presented increased body weight, adiposity and cholesterol in the groups descending from the F0 generation that consumed a HS/HF diet (DHSed2). This was not observed in females. This study thus demonstrates the transgenerational effect of the sucrose- and lipid-rich diet and the physical treadmill training prior to pregnancy.

The HS/HF diet offered to sedentary mothers led to increased adiposity and body weight and glycemia in F1 males and females. Concerning the effects of exercise performed by mothers in both the CExe control group and DHExe diet group, decreased body weight, adiposity and glycemia were observed both in females and males. In addition, males also experienced improvements in triglyceride levels.

The results also indicate that a maternal high-fat and simple carbohydrates diet causes glucose intolerance in males and indicated that maternal physical training was effective in preventing these harmful effects in both males and females. This is corroborated by the study carried out by Stanford et al.,^{Reference Stanford, Lee, Getchell, So, Hirshman and Goodyear12} who recently demonstrated that C57/Bl6 mice born from mothers consuming 60 % high-fat diet and placed in cages with running wheels before and during pregnancy presented improvements in the glucose tolerance test, suggesting that offspring were protected against maternal diet-induced glucose intolerance.

For F2, the results were more evident in males compared to females. Exercise effects on body weight and total cholesterol reduction were observed in females. In males, aside from a significant increase in weight, adiposity and cholesterol in the group whose F0 generation ingested a HS/HF diet, exercise was effective in improving both lipid and adiposity profiles.

A possible aerobic training-derived mechanism is ATP regeneration capacity, which increases mitochondrial enzymatic activity, mitochondrial density and oxygen consumption.^{Reference Taylor, McConnell and Khan35,Reference Kirchner, Osler, Krook and Zierath36} Epigenetic changes occur in skeletal muscle due to decreases in intracellular oxygen concentrations during exercise. In addition, physical training activates the intracellular peroxisome proliferator-activated receptor coactivator-1α (PGC-1 α) pathway, which is considered an energetic metabolism regulator in skeletal muscle and adipose tissue. It is also responsible for increasing mitochondria biogenesis,^{Reference Laker, Connelly and Yan37–Reference Ribeiro, Tófolo and Martins39} protecting offspring from obesity, Type 2 diabetes mellitus and any harmful effects derived from a high-fat diet consumed by the maternal generation.^{Reference Raipuria, Bahari and Morris23,Reference Mathias, Elmhiri and de Oliveira40}

One of the consequences of hypercaloric, hypolipemic or hyperglycemic diet consumption during pregnancy and lactation is a glycemic profile alteration in adult descendants.^{Reference Paes, Gonçalves and Terra6,Reference Armitage, Khan, Taylor, Nathanielsz and Poston41–Reference Zambrano and Nathanielsz43} Modulation of pancreatic β-cells may also occur, implying in glycemia alterations.^{Reference El-Assaad, Buteau and Peyot44}

Physical exercise performed by the maternal generation reduced plasma glucose levels of their progeny, possibly due to enhanced glucose uptake by skeletal muscles.^{Reference Raipuria, Bahari and Morris23} Other studies have also reported the same effect in F1 progeny, in which maternal exercise reduced plasma glucose concentrations, more effective in males than in females, and that such an effect was associated with increased glucose transporter type 4 (GLUT4) levels in skeletal muscle.^{Reference Stanford, Lee, Getchell, So, Hirshman and Goodyear12,Reference Vega, Reyes-Castro, Bautista, Larrea, Nathanielsz and Zambrano24}

Results from other studies have indicated that acute and chronic exercise effects in rats lead to increases in PGC1α expression in white adipose tissue,^{Reference Raipuria, Bahari and Morris23,Reference Sutherland, Bomhof, Capozzi, Basaraba and Wright45} capable of limiting visceral fat accumulation and reducing circulating triglyceride levels.^{Reference Sheldon, Nicole Blaize and Fletcher21,Reference Vega, Reyes-Castro, Bautista, Larrea, Nathanielsz and Zambrano24,Reference Eisele and Handschin46} Thus, it has been demonstrated herein that chronic physical exercise performed leads to a protective effect in subsequent generations.