Introduction
Feeding behavior can be defined as the psychobiological aspects related to food choices, frequency and duration of meals, as well as in other aspects the complex interaction between homeostatic and hedonic mechanisms in relation to the environment Reference Liu and Kanoski1,Reference Gahagan2 . Food intake represents a component of homeostatic feeding behavior and represents the amount of food ingested by an individual Reference Roh and Kim3 . The regulation of food intake occurs centrally in the hypothalamus, a structure composed of nuclei formed by subpopulations of orexigenic and anorectic neurons that control the energy balance Reference Roh and Kim3 . These neurons express molecules, such as pro-opiomelanocortin and agouti-related peptide (AgRP), which modulate caloric intake and energy expenditure Reference Liu and Kanoski1 . Thus, hypothalamic cells act as nutritional sensors in response to energy status in body, playing an important role in obesity pathophysiology Reference Elizondo-Vega, Recabal and Oyarce4 .
Obesity in humans is characterized by body mass index ≥ 30 kg/m2, associated with an excessive accumulation of fat in abdominal region Reference Redinger5,Reference Müller and Geisler6 . Studies reveal that obesity has tripled since 1975, reaching more than 650 million adults and 45 million children worldwide in 2016, becoming a pandemic Reference Bentham, Di Cesare and Bilano7 . The increase in prevalence of obesity is also due to increased availability and consumption of processed foods rich in saturated fat, refined sugars, and sodium, considered palatable foods Reference Cordain, Eaton and Sebastian8-Reference Fox, Feng and Asal10 . This dietary profile has favored the early onset of type 2 diabetes mellitus, hypertension, and obesity, which represent potential programmers of deleterious effects on offspring health Reference Márquez-Valadez11,Reference Jones, Jurgens and Evans12 . Thus, experimental studies with maternal hyperlipidic experimental diets try to understand the mechanisms involved in these outcomes Reference Alfaradhi and Ozanne13,Reference Sullivan, Smith and Grove14 .
In this current health context, during some critical developmental stages, such as pregnancy and lactation, offspring may have a greater predisposition to obesity and its comorbidities Reference Desai and Hales15 . The perinatal period is a critical phase marked by the formation of organs and systems through gene expression, cellular hyperplasia, and hypertrophy Reference Morgane, Austin-LaFrance and Bronzino16 . In this stage of development, the mother–child binomial is most vulnerable to external modulations, such as maternal feeding Reference Alfaradhi and Ozanne13 . Exposure to a high-fat diet (HFD) represents a model of maternal obesity induction and causes morphological, behavioral, and cellular changes in offspring Reference Siddeek, Mauduit and Chehade17,Reference Glendining, Fisher and Jasoni18 . This excessive maternal nutrient intake disrupts eating behavior, especially dietary intake and preference, affecting the offspring’s weight and body composition Reference Alfaradhi and Ozanne13,Reference Sullivan, Nousen and Chamlou19,Reference Chang, Gaysinskaya and Karatayev20 . Thus, this systematic review evaluated the repercussions of maternal perinatal exposure to HFDs on offspring feeding behavior and body composition.
Material and methods
For the elaboration of this systematic review, the authors followed the recommendations present in the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA Statement). Our systematic review was carried out by publication of protocol in the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) platform, with free access to interested parties.
Search strategy
The search and selection of articles was conducted by two independent reviewers (Chaves, W. F. and Silva, J. M.) and performed in the LILACS, Web of Science, SCOPUS, and PUMBED databases in February 2019. In searching the databases, the following MESH (Medical Subject Headings) terms were applied: “high-fat diet,” “maternal exposure,” “pregnancy,” “lactation,” and “feeding behavior”. Duplicates were removed from the articles retrieved through the searches. Initially, titles and summaries were screened, following by assessment of full texts for eligibility against our pre-specified inclusion/exclusion criteria. Any disagreements between the researchers were resolved by consulting a third independent reviewer (Pinheiro, I. L.).
Eligibility criteria
The population of interest was limited to pups from mothers exposed to a HFD during gestation and/or lactation, rodents of any species, sex, and age. Our first outcome included all types of feeding behavior evaluation. Subsequently, articles were searched for information on body weight or body composition assessment. There were no year nor language limitations for the inclusion of studies. Articles that did not present the criteria of population eligibility, intervention, comparison, and outcomes were excluded (Table 1).
Table 1. Eligibility criteria applied in this study
Data extraction
The data extraction was performed after the complete reading of articles previously selected according to the eligibility criteria by two independent researchers. The third researcher was consulted when there were differences or doubts. The key data were collected, such as names of authors, year of publication, species of animal, composition of diets, intervention period, post-weaning diet, parameters analyzed, and main offspring results. The data were transcribed into a table according to outcomes, these being feeding behavior or somatic/body composition.
Assessment of methodology quality
The evaluation of methodological quality of studies included in this systematic review was performed using the tool known as SYRCLE risk of bias (RoB) Reference Hooijmans, Rovers and De Vries21 . The tool was applied individually to the articles included and independently by the reviewers. The SYRCLE RoB consists of 10 questions related to random sequence generation, baseline characteristics, allocation concealment, random housing, blinding of participants and personnel, random outcome data, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. These questions were judged as having high, uncertain, or low RoB. The Kappa test was applied after this phase to measure the level of agreement in the assessment of RoB between the first and second reviewers. The information from this step was synthesized through a figure obtained with Review Manager software version 5.3, also used in the elaboration of study flowchart (Fig. 1).
Fig. 1. Flowchart of study selection process applied in the present study.
Fig. 2. Risk of bias (RoB) summary of studies: review authors’ judgments about each RoB item for each included article. + (green) low RoB, − (red) high RoB, and ? (yellow) unclear RoB. (For interpretation of references to color in this figure, the reader is referred to the web version of this article.)
Results
During the first stage in searching the electronic databases (Web of Science, PUBMED, Lilacs, and SCOPUS) a total of 3356 articles were found. Subsequently, 1316 duplicates were removed. A total of 2040 articles had titles and abstracts screened from which 1934 articles were eliminated because they did not address the eligibility criteria (Table 1) in the title and abstract. Full text was read in 106 articles, with then being excluded 89 articles through the exclusion criteria (Table 1). All articles found were published in English. The steps of conducting the research are described in the flowchart below (Fig. 1).
Assessment of quality of studies
The evaluation of RoB applied between the reviewers resulted in Kappa = 0.65, classified as substantial level of agreement Reference Landis and Koch22 (Fig. 2). In the studies, seven authors reported randomizing the animals Reference Camacho, Montalvo-Martinez and Cardenas-Perez23-Reference Segovia, Vickers and Gray29 . In relation to the baseline characteristics, eight articles did not report the baseline characteristics of their subjects in the text Reference Reynolds, Segovia and Zhang28,Reference Kozak, Mercer and Burlet30-Reference Yokomizo, Inoguchi and Sonoda36 . None of the articles recorded the procedure for blinding the allocation of animals to groups. The researchers responsible for data collection were not reported in any of included articles. No article was clear about randomization in accommodation or selection of animals for collection of results. The article by Kojima, Catavaro, and Rinaman presented the criteria for exclusion of animals from experimental groups in the evaluation of the results Reference Kojima, Catavero and Rinaman37 . Five articles presented a selection of results Reference Melo, Benatti and Ignacio-Souza26,Reference Segovia, Vickers and Gray29,Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Yokomizo, Inoguchi and Sonoda36,Reference Nakashima38 . Finally, other types of risks of bias were identified in four articles for lack of important information such as mating procedure, adaptation to diets, characteristics, and environment of vivarium Reference Lemes, de Souza and Payolla25,Reference Rahman, Ullah and Ke27,Reference Kojima, Catavero and Rinaman37,Reference Sun, Liang and Ewald39 .
Methodological profile of studies
The studies included used the following types of rodents: Sprague-Dawley (n = 7) Reference Rahman, Ullah and Ke27-Reference Segovia, Vickers and Gray29,Reference Treesukosol, Sun and Moghadam32,Reference Kojima, Catavero and Rinaman37-Reference Sun, Liang and Ewald39 , Wistar (n = 2) Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Cardenas-Perez, Fuentes-Mera and De La Garza24 , Long Evans (n = 1) Reference Kozak, Mercer and Burlet30 , C57BL/6 (n = 4) Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33,Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Yokomizo, Inoguchi and Sonoda36 , Swiss (n = 2) Reference Lemes, de Souza and Payolla25,Reference Melo, Benatti and Ignacio-Souza26 , and FVB albino mice (n = 1) Reference Turdi, Ge and Hu34 . Ten articles evaluated the male offspring (n = 10). Several studies used only females pups (n = 3) or both sexes (n = 4). The nutritional manipulation was performed through diets with a caloric contribution of lipids ranging from 10% to 19% for control diet versus 30% to 76% for HFDs. This manipulation was more frequent during gestation and lactation (n = 15) Reference Camacho, Montalvo-Martinez and Cardenas-Perez23-Reference Melo, Benatti and Ignacio-Souza26,Reference Reynolds, Segovia and Zhang28-Reference Treesukosol, Sun and Moghadam32,Reference Turdi, Ge and Hu34-Reference Sun, Liang and Ewald39 , but there were also interventions only at gestation (n = 1) Reference Rahman, Ullah and Ke27 or lactation (n = 1) Reference Tsuduki, Yamamoto and Shuang33 . Only comparisons of offspring of groups fed on a control diet after weaning, except the articles that evaluated food search, were selected. All articles included (n = 17) presented some proposed feeding behavior-related outcomes, but two articles did not show defined body composition outcomes (n = 15) Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33-Reference Sun, Liang and Ewald39 . Food intake (n = 10) Reference Camacho, Montalvo-Martinez and Cardenas-Perez23-Reference Reynolds, Segovia and Zhang28,Reference Tsuduki, Yamamoto and Shuang33-Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Sun, Liang and Ewald39 , caloric intake (n = 6) Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Segovia, Vickers and Gray29,Reference Kozak, Mercer and Burlet30,Reference Treesukosol, Sun and Moghadam32,Reference Tsuduki, Yamamoto and Shuang33,Reference Yokomizo, Inoguchi and Sonoda36 , food preference (n = 4) Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Treesukosol, Sun and Moghadam32,Reference Nakashima38 , and independent feeding (n = 1) Reference Kojima, Catavero and Rinaman37 were used to evaluate outcomes related to components of feeding behavior. Other outcomes were obtained by measuring body weight (n = 15) Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33-Reference Sun, Liang and Ewald39 , body composition (n = 12) Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Segovia, Vickers and Gray29,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33-Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Nakashima38,Reference Sun, Liang and Ewald39 , and body length (n = 1) Reference Rahman, Ullah and Ke27 .
Main results on offspring feeding behavior
The results of outcomes related to feeding behavior were described according to the analyzed parameters (Table 2). Food intake was the most frequently mentioned outcome, but presented high variability in results among the articles selected. Melo et al. and Lemes et al. showed an increase in food intake in young males from HFD mothers Reference Lemes, de Souza and Payolla25,Reference Melo, Benatti and Ignacio-Souza26 . Rahman et al. also found an increase in food intake in young males, but from mothers exposed to HFD only during pregnancy Reference Rahman, Ullah and Ke27 . Cardenas-Perez et al., on the other hand, did not observe difference of food intake in young females from HFD mothers Reference Cardenas-Perez, Fuentes-Mera and De La Garza24 . Long-term evaluation showed hyperphagia in both male and female offspring whose mothers had been exposed to HFD in the perinatal period according to Sun et al. (the males) and Reynolds et al. (the females) Reference Reynolds, Segovia and Zhang28,Reference Sun, Liang and Ewald39 . On the other hand, Volpato et al., Turdi et al., Tsuduki et al., and Camacho et al. did not find any difference in long-term food intake for either male or female offspring from HFD mothers Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Tsuduki, Yamamoto and Shuang33-Reference Volpato, Schultz and Magalhães-Da-Costa35 . Caloric intake made no difference between groups according to Yokomizo et al., Tsuduki et al., Segovia et al., and Cardenas-Perez et al. Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Segovia, Vickers and Gray29,Reference Tsuduki, Yamamoto and Shuang33,Reference Yokomizo, Inoguchi and Sonoda36 . In contrast, Kozak et al. showed a reduction in caloric intake in young females from HFD mothers Reference Kozak, Mercer and Burlet30 .
Table 2. Summary of main results in feeding behavior
Higher preference for palatable foods such as sweetened drinks, alcohol, and HFDs was observed when food preference for offspring from HFD mothers was evaluated. These results were evidenced over the long term in both male and female offspring, according to Nakashima, Treesukosol et al., Peleg-Raibstein et al., and Camacho et al. Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Treesukosol, Sun and Moghadam32,Reference Nakashima38 . The independent feeding test has as its main objective to identify the beginning of a search for solid foods during lactation in the food transition phase. Kojima, Catavero, and Rinaman found that offspring from HFD mothers started earlier to search and eat their mothers solid food than offspring from the control mothers Reference Kojima, Catavero and Rinaman37 .
Main results in the offspring body composition
Offspring somatic growth is a complementary result that helps understanding the repercussions caused by changes in feeding behavior (Table 3). Body weight is the secondary outcome most frequently evaluated in included studies. Regarding birthweight, Melo et al., Reynolds et al., and Lemes et al. observed that offspring from HFD mothers had low birthweight compared to offspring from the control group Reference Lemes, de Souza and Payolla25,Reference Melo, Benatti and Ignacio-Souza26,Reference Reynolds, Segovia and Zhang28 . However, Yokomizo et al. and Kojima, Catavero, and Rinaman reported that pups from HFD mothers were heavier at birth Reference Yokomizo, Inoguchi and Sonoda36,Reference Kojima, Catavero and Rinaman37 . Nakashima and Volpato et al. did not identify differences in body weight and birthweight in young male rodents from HFD mothers Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Nakashima38 . Kozak et al. were the only author that reported lean animals from HFD mothers during lactation Reference Kozak, Mercer and Burlet30 . All authors who evaluated body weight over a long term reported an increase in this parameter from weaning until adulthood in offspring from HFD mothers Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Rahman, Ullah and Ke27-Reference Segovia, Vickers and Gray29,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Turdi, Ge and Hu34,Reference Sun, Liang and Ewald39 .
Table 3. Summary of main results in body composition
Body fat weight and fat distribution on the body are representative parameters in evaluation of body composition in laboratory animals. Young animals from HFD mothers presented most deposition of body fat, especially in the retroperitoneal, mesenteric, and epididymal areas, according to five articles Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Reynolds, Segovia and Zhang28 . In other studies, a similar pattern was found for fat deposition in adult rodents of both sexes Reference Segovia, Vickers and Gray29,Reference Tsuduki, Yamamoto and Shuang33-Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Sun, Liang and Ewald39 . In contrast, Nakashima was the only author that did not observe significant difference in body composition in young offspring from HFD mothers Reference Nakashima38 . Rahman et al. were the only researcher to measure body length and identified that young offspring from HFD mothers were larger than the control animals Reference Rahman, Ullah and Ke27 .
Discussion
The main results of the articles included in this systematic review describe changes in feeding behavior and body composition in offspring, promoted by maternal HFDs during the perinatal period. Regarding the outcomes in feeding behavior, the offspring of HFD mothers were reported to have increased food intake in the young animals Reference Lemes, de Souza and Payolla25-Reference Reynolds, Segovia and Zhang28,Reference Sun, Liang and Ewald39 but not maintained in adulthood Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Turdi, Ge and Hu34,Reference Volpato, Schultz and Magalhães-Da-Costa35 . On the other hand, in studies that evaluated caloric intake, there was no difference between groups of different ages Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Segovia, Vickers and Gray29,Reference Tsuduki, Yamamoto and Shuang33,Reference Yokomizo, Inoguchi and Sonoda36 . Greater preference for palatable foods (rich in sugars, fat, and sodium) in offspring of mothers exposed to HFD during pregnancy and lactation was observed Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Treesukosol, Sun and Moghadam32,Reference Nakashima38 . Feeding independence occurred earlier in the offspring of HFD mothers Reference Kojima, Catavero and Rinaman37 . Increased body weight Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Segovia, Vickers and Gray29,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33,Reference Turdi, Ge and Hu34,Reference Yokomizo, Inoguchi and Sonoda36,Reference Kojima, Catavero and Rinaman37,Reference Sun, Liang and Ewald39 , length Reference Rahman, Ullah and Ke27 , and changes in body composition through increased long-term fat deposition Reference Cardenas-Perez, Fuentes-Mera and De La Garza24-Reference Segovia, Vickers and Gray29,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Tsuduki, Yamamoto and Shuang33-Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Sun, Liang and Ewald39 were also observed in these offspring.
The increase in food intake found in this review reveals possible early changes in the regulation of energy homeostasis on offspring Reference Lemes, de Souza and Payolla25-Reference Rahman, Ullah and Ke27,Reference Bae-Gartz, Janoschek and Breuer40 . Significant orexigenic signaling is observed by increasing the density of neuropeptide Y (NPY)/AgRP-expressing neurons in the arched and paraventricular nuclei of the hypothalamus in offspring of mothers fed a HFD Reference Chang, Gaysinskaya and Karatayev20,Reference Lemes, de Souza and Payolla25 . This set of morphofunctional changes that occur in the hypothalamus promotes hyperphagic behavior, also impacting body composition and glycemic control in offspring Reference Chang, Gaysinskaya and Karatayev20 . In association, offspring present hypothalamic resistance to neural and humoral satiety signals, such as serotonin, leptin, and insulin Reference Lemes, de Souza and Payolla25,Reference Bae-Gartz, Janoschek and Breuer40 .
Systemic inflammation and oxidative stress represent two of the main mechanisms that trigger the maternal programming effect on food intake Reference Alfaradhi and Ozanne13 . The first traces of deleterious effects caused by maternal HFD occur during pregnancy, when there is an increased expression of tumor necrosis factor alpha (TNF-α) in fetal tissues as well as insulin resistance Reference Sullivan, Nousen and Chamlou19,Reference Murabayashi, Sugiyama and Zhang41 . Maternal exposure to HFD affects the expression of inflammatory cytokines and free radicals in immune cells such as microglia Reference Mendes, Kim and Velloso42 . In the placenta, immune cells express Toll-like 4 receptors that increase the concentration of inflammatory mediators such as TNF-α and interleukins 1β, 6, and 17 in response to exposure to the HFD diet Reference Kim, Young and Grattan43,Reference Yang, Li and Haghiac44 .
Maternal exposure influences the offspring’s food choice, such as the preference for palatable foods (rich in sugars, fat, and/or sodium) in adulthood Reference Sullivan, Smith and Grove14,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Treesukosol, Sun and Moghadam32,Reference Nakashima38,Reference Dias-Rocha, Almeida and Santana45 . This response, generated by maternal programming, could be related to increased hypothalamic expression of endocannabinoid receptors (CB1 and CB2) in offspring, regardless of gender, accompanied by an increase in palatable food intake during the dietary preference tests Reference Dias-Rocha, Almeida and Santana45,Reference Ramírez-López, Arco and Decara46 . Disorders in the dopaminergic signaling pathways are also observed in offspring after maternal exposure to palatable diets Reference Reyes47 . Dopamine and its receptors (D1 and D2) regulate reward system responses. The maternal HFD diet promotes methylation of dopaminergic and cannabinoid system genes by increasing their expression Reference Vucetic, Kimmel and Totoki48 .
In addition, some methodological variances among articles may explain some differences among the research results regarding food intake. Maternal HFD protocols containing 30–45% kcal/lipids did not promote changes in food intake Reference Camacho, Montalvo-Martinez and Cardenas-Perez23,Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Segovia, Vickers and Gray29,Reference Tsuduki, Yamamoto and Shuang33,Reference Turdi, Ge and Hu34 . In these studies, when the offspring were exposed to additional factors, such as re-exposure to HFD or isolation stress, changes in food intake were observed Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Tsuduki, Yamamoto and Shuang33,Reference Turdi, Ge and Hu34 . Furthermore, that dietary protocol seems not to have promoted inflammation or changes in mitochondrial genes in the offspring’s hypothalamus, factors related to impaired regulation of food intake Reference Cardenas-Perez, Fuentes-Mera and De La Garza24,Reference Segovia, Vickers and Gray29 . On the other hand, protocols containing 46–60% kcal/lipids were more effective in the development of hyperphagia in offspring Reference Lemes, de Souza and Payolla25-Reference Rahman, Ullah and Ke27,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Treesukosol, Sun and Moghadam32,Reference Sun, Liang and Ewald39 . The maternal diet was the main stimulus that induced leptin resistance, increased proliferation of NPY neurons, and their gene expression Reference Lemes, de Souza and Payolla25,Reference Melo, Benatti and Ignacio-Souza26 . Diets with kcal/lipid content greater than 60% showed inconclusive effects on the offspring’s food intake Reference Kozak, Mercer and Burlet30,Reference Yokomizo, Inoguchi and Sonoda36 . Additionally, these protocols did not promote changes in the expression and proliferation of NPY neurons in different hypothalamic nucleus, with hyperphagia only related to re-exposure to HFD Reference Kozak, Mercer and Burlet30,Reference Yokomizo, Inoguchi and Sonoda36 .
Low birthweight in offspring of HFD mothers was evidenced in this systematic review Reference Lemes, de Souza and Payolla25,Reference Melo, Benatti and Ignacio-Souza26,Reference Reynolds, Segovia and Zhang28 . Adequate intrauterine development is dependent on maternal nutrition, placental functioning, and trophic signs Reference Bloomfield, Spiroski and Harding49 . Given this, intake of HFD diets by the parent may cause a nutritional and inflammatory imbalance that compromises fetal-placental circulation and may restrict offspring growth Reference Frias, Morgan and Evans50 . This condition predisposes the mother to develop preeclampsia, a complication characterized by hypertension and endothelial dysfunctions in the placental vessels capable of compromising the supply of nutrients to the fetus Reference Harmon, Cornelius and Amaral51,Reference Hayes, Lechowicz and Petrik52 . This makes the offspring susceptible to low birthweight, prematurity, and lower perinatal survival rate Reference Hayes, Lechowicz and Petrik52,Reference Meijnikman, Gerdes and Nieuwdorp53 .
Increased white adipose tissue (WAT) deposition in pads represents the most frequent change in body composition caused by fetal programming by maternal HFD. In offspring, fat oxidation attained in the process of cellular respiration in metabolic tissues such as skeletal muscle and brown adipose tissue (BAT) is impaired Reference Glendining, Fisher and Jasoni18,Reference Liang, Yang and Zhang54 . In consequence, there is a reduction in energy expenditure caused by the reduction in lean mass percentage in association with changes in mitochondrial protein expression Reference Khamoui, Desai and Ross55 . In metabolic tissues, mitochondrial dysfunction occurs by reducing the expression of UCP-1, Pgc1, and Cox7a1, uncoupling proteins that play a key role in the progress of the thermogenesis process Reference Liang, Yang and Zhang54,Reference Borengasser, Faske and Kang56 . Another aggravating factor is the increase of populational density of the NPY and AgRP neurons in the hypothalamus favoring BAT inhibition, contributing to the positive energy balance and WAT surplus energy stock Reference Lemes, de Souza and Payolla25,Reference Zhang, Cline and Gilbert57,Reference White, Purpera and Morrison58 .
In relation to body weight, the HFD (76% kcal/lipids) protocol used by Kozak et al. promoted a reduction in the offspring’s body weight during lactation. This result can be associated with the capacity of maternal HFDs, such as ketogenic diets, to stimulate weight loss by favoring the oxidation of body fat reserves Reference Sussman, Ellegood and Henkelman59 . On the other hand, the absence of difference in body weight observed by Nakashima may be related to measurement at specific ages; preference for HFD observed in animals could influence the increase in body weight over the long term, as observed in other articles Reference Segovia, Vickers and Gray29,Reference Peleg-Raibstein, Sarker and Litwan31,Reference Sun, Liang and Ewald39 . Birthweight was an inconclusive result in the articles by Kojima, Catavero, and Rinaman and Volpato et al. Despite this, insulin resistance, fat deposition in the liver, and increased triglycerides were observed at birth, relevant changes that can lead to later development of obesity and metabolic syndrome Reference Volpato, Schultz and Magalhães-Da-Costa35,Reference Kojima, Catavero and Rinaman37 .
Conclusion
Maternal exposure to HFD during pregnancy and/or lactation can modify the feeding behavior in offspring from HFD mothers. In young animals, an increase in food intake was identified, with no change in caloric intake over the short term. Greater preference for palatable foods, however, persisted over the long term in these animals. In addition, despite low birthweight, offspring had increased body weight and deposition of WAT over the long term.
Acknowledgments
None.
Financial support
This article was financially supported by CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, Brazil) with project numbers 425743/2018-7 and 408506/2016-4.
Conflict of interest
None.
Ethical Standards
None.
