scholarly journals Maternal High-Fat–High-Carbohydrate Diet-Induced Obesity Is Associated with Increased Appetite in Peripubertal Male but Not Female C57Bl/6J Mice

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2919 ◽  
Author(s):  
Debra Kulhanek ◽  
Rachel Weigel ◽  
Megan E. Paulsen

Diet-induced maternal obesity might play a critical role in altering hypothalamic development, predisposing the offspring to obesity and metabolic disease later in life. The objective of this study was to describe both phenotypic and molecular sex differences in peripubertal offspring energy homeostasis, using a mouse model of maternal obesity induced by a high-fat–high-carbohydrate (HFHC) diet. We report that males, not females, exposed to a maternal HFHC diet had increased energy intake. Males exposed to a maternal HFHC diet had a 15% increased meal size and a 46% increased frequency, compared to the control (CON) males, without a change in energy expenditure. CON and HFHC offspring did not differ in body weight, composition, or plasma metabolic profile. HFHC diet caused decreased hypothalamic glucocorticoid expression, which was further decreased in males compared to females. Maternal weight, maternal caloric intake, and male offspring meal frequency were inversely correlated with offspring hypothalamic insulin receptor (IR) expression. There was a significant interaction between maternal-diet exposure and sex in hypothalamic IR. Based on our preclinical data, we suggest that interventions focusing on normalizing maternal nutrition might be considered to attenuate nutritional influences on obesity programming and curb the continuing rise in obesity rates.

2019 ◽  
Vol 317 (3) ◽  
pp. E526-E534 ◽  
Author(s):  
Marianna Sadagurski ◽  
Lucas Kniess Debarba ◽  
Joao Pedro Werneck-de-Castro ◽  
Abear Ali Awada ◽  
Tess A. Baker ◽  
...  

Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1572
Author(s):  
Sofiane Safi-Stibler ◽  
Etienne A. Thévenot ◽  
Luc Jouneau ◽  
Mélanie Jouin ◽  
Alexandre Seyer ◽  
...  

Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC–HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring’s metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, including 1,5-anhydroglucitol, saccharopine and β-hydroxybutyrate, differential in the three tissues. Moreover, maternal diet had a unique impact on the abundance of two metabolites in the liver. Particularly, anserine abundance, lowered by maternal obesity, was normalized by a preconceptional weight loss, whatever the post-weaning diet. This study is the first to identify a programming long-term effect of maternal preconception obesity on the offspring metabolome.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 68-68
Author(s):  
Kjersti M Aagaard

Abstract Human microbial communities are characterized by their metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. We are only beginning to characterize the complex set of interactions which alters both community membership and function in early development. With respect to the potential source of microbiota at birth, it has been generally assumed that the majority of seeding microbes originate from the maternal lower genital tract, with microbiota ascending into the otherwise sterile intrauterine. However, we and subsequently others have recently demonstrated that (1) the vaginal and gut microbiome communities are distinctly structured in pregnancy, and (2) the intrauterine environment and the fetus is in fact not sterile, but rather harbors a low-abundance microbiome which varies by several measured exposures, and (3) the maternal diet during both gestation and lactation, and notably a high fat diet, has a particularly strong impact on the developing and early in life microbial community structure. We have taken two dynamic approaches to answering these questions in our studies. First, we use large and robust longitudinal cohorts of maternal-infant dyads collected across gestation and into infancy to gain deeper insight into both source and sink of the early developmental microbiome and its role on determining length of gestation. Second, we utilize our well established primate models of maternal high fat dietary exposure, both in the absence and presence of maternal obesity, to determine the impact of maternal diet on both the microbiome and the resultant offspring metabolic phenotype.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1022-1022
Author(s):  
Hunter Korsmo ◽  
Moshe Dembitzer ◽  
Sarah Khaldi ◽  
Shameera Sheeraz ◽  
Juliet Kosichenko ◽  
...  

Abstract Objectives This study investigated whether maternal choline supplementation (MCS) could reduce the chronic metabolic stress that is induced by prenatal maternal obesity and postnatal Western Diet (WD) feeding. Methods C57BL/6 dams were either fed a normal fat (NF, 10 kcal %fat) control diet or a high fat (HF, 45 kcal % fat) diet prior to, during pregnancy and during lactation. These dams received either 25 mM choline or plain drinking water. After weaning, offspring were fed the WD diet (45 kcal %fat, 34 kcal %fructose, and 0.25% cholesterol) for 16 weeks before glucose tolerance testing and dissection. Results After 16 weeks of WD feeding, offspring from normal-fat, choline supplemented fed (MCS-NF) dams are protected from weight gain compared to offspring from dams fed a high-fat diet with or without choline supplementation (MCS-HF or MCO-HF)(P < 0.043). Male offspring from MCS-NF fed dams have reduced caloric intake (P < 0.019) and reduced gene expression of Acc1 which mediates liver de novo fatty acid synthesis (P = 0.005) compared to the non-supplemented normal-fat dams (MCO-NF) after 16 weeks of WD feeding. Female offspring from MCS-HF fed dams have lower fasting glucose levels compared to MCO-HF fed dams after 16 weeks of WD feeding (P = 0.034). Conclusions MCS mitigates some pathological hallmarks that are induced by prolonged WD feeding in offspring. Funding Sources NIGMS.


Author(s):  
Kinga Gawlińska ◽  
Dawid Gawliński ◽  
Małgorzata Filip ◽  
Edmund Przegaliński

Abstract A balanced maternal diet is essential for proper fetal development, and the consumption of a nutritionally inadequate diet during intrauterine development and early childhood is associated with a significantly increased risk of metabolic and brain disorders in offspring. The current literature indicates that maternal exposure to a high-fat diet exerts an irreversible influence on the general health of the offspring. This review of preclinical research examines the relationship between a maternal high-fat diet during pregnancy or lactation and metabolic changes, molecular alterations in the brain, and behavioral disorders in offspring. Animal models indicate that offspring exposed to a maternal high-fat diet during pregnancy and lactation manifest increased depressive-like and aggressive behaviors, reduced cognitive development, and symptoms of metabolic syndrome. Recently, epigenetic and molecular studies have shown that maternal nutrition during pregnancy and the suckling period modifies the development of neurotransmitter circuits and many other factors important to central nervous system development. This finding confirms the importance of a balanced maternal diet for the health of offspring.


1990 ◽  
Vol 258 (2) ◽  
pp. E347-E351 ◽  
Author(s):  
W. G. Abbott ◽  
B. V. Howard ◽  
G. Ruotolo ◽  
E. Ravussin

A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin-dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high-carbohydrate diet.


2019 ◽  
Vol 11 (3) ◽  
pp. 273-284
Author(s):  
Kyle J. Mamounis ◽  
Naomi R. Shvedov ◽  
Nicholas Margolies ◽  
Ali Yasrebi ◽  
Troy A. Roepke

AbstractThe early-life origins of disease hypothesis has been applied to obesity research and modeled through overnutrition, usually with a high-fat diet (HFD). Since the obesity epidemic coincided with societal change in dietary fat consumption, rather than amount, manipulation of fatty acid (FA) profile is an under-investigated area of study. Additionally, the binding of FAs to nuclear receptors may have persistent intergenerational, extranutritive endocrinological effects that interact with the actions of reproductive steroids causing sex-dependent effects. To determine the role of FA type in the effects underlying maternal HFD, we fed wild-type C57BL6/J mating pairs, from preconception through lactation, a HFD with high saturated fat levels from coconut oil or high linoleic acid (LA) levels from vegetable oil. Male and female offspring body weight and food intake were measured weekly for 25 weeks. Assays for glucose metabolism, body composition, and calorimetry were performed at 25 weeks. Plasma metabolic peptides and liver mRNA were measured terminally. Obesity was primarily affected by adult rather than maternal diet in males, yet in females, maternal HFD potentiated the effects of adult HFD. Maternal HFD high in LA impaired glucose disposal in males weaned onto HFD and insulin sensitivity of females. Plasma leptin correlated with adiposity, but insulin and insulin receptor expression in the liver were altered by maternal LA in males. Our results suggest that maternal FA profile is most influential on offspring glucose metabolism and that adult diet is more important than maternal diet for obesity and other parameters of metabolic syndrome.


2014 ◽  
Vol 307 (3) ◽  
pp. R299-R309 ◽  
Author(s):  
Dalila Azzout-Marniche ◽  
Catherine Chaumontet ◽  
Nachiket A. Nadkarni ◽  
Julien Piedcoq ◽  
Gilles Fromentin ◽  
...  

Obesity-prone (OP) rodents are used as models of human obesity predisposition. The goal of the present study was to identify preexisting defects in energy expenditure components in OP rats. Two studies were performed. In the first one, male Wistar rats ( n = 48) were fed a high-carbohydrate diet (HCD) for 3 wk and then a high-fat diet (HFD) for the next 3 wk. This study showed that adiposity gain under HCD was 2.9-fold larger in carbohydrate-sensitive (CS) than in carbohydrate-resistant (CR) rats, confirming the concept of “carbohydrate-sensitive” rats. Energy expenditure (EE), respiratory quotient (RQ), caloric intake (CI), and locomotor activity measured during HFD identified no differences in EE and RQ between fat-resistant (FR) and fat-sensitive (FS) rats, and indicated that obesity developed in FS rats only as the result of a larger CI not fully compensated by a parallel increase in EE. A specific pattern of spontaneous activity, characterized by reduced activity burst intensity, was identified in FS rats but not in CS ones. This mirrors a previous observation that under HCD, CS but not FS rats, exhibited bursts of activity of reduced intensity. In a second study, rats were fed a HFD for 3 wk, and the components of energy expenditure were examined by indirect calorimetry in 10 FR and 10 FS rats. This study confirmed that a low basal EE, reduced thermic effect of feeding, defective postprandial energy partitioning, or a defective substrate utilization by the working muscle are not involved in the FS phenotype.


2009 ◽  
Vol 296 (5) ◽  
pp. R1464-R1472 ◽  
Author(s):  
Christy L. White ◽  
Megan N. Purpera ◽  
Christopher D. Morrison

We tested the hypothesis that maternal consumption of dietary fat, independent from obesity, increases serum leptin in neonatal pups and predisposes them to adult obesity. Female rats either were fed a high-fat (HF) diet or a low-fat (LF) diet or were fed the HF diet but pair fed (PF) to the caloric intake of the LF group for 4 wk before breeding and throughout gestation and lactation. Dams consuming the HF diet had increased adiposity and were hyperphagic. At weaning, pups born to obese dams had significantly higher body fat and serum leptin levels and reduced insulin tolerance compared with offspring of LF-fed dams. Pups were weaned onto a chow diet until 8 wk of age, when they were then fed either HF or LF diet. At 18 wk of age, offspring from obese HF dams weighed more than offspring from nonobese LF or PF dams, and offspring eating HF diet weighed significantly more than those eating LF diet. Consequently, HF-fed offspring of obese HF dams weighed the most and LF-fed offspring from obese HF dams were similar in weight to HF-fed offspring from nonobese LF dams. These data suggest that maternal obesity exerts an independent effect on offspring body weight that is of similar magnitude as the effect of the offspring's adult diet. Furthermore, there was no difference in body weight between the nonobese LF and PF offspring on either diet. Together, these data suggest that maternal adiposity, and not dietary fat per se, induces hyperleptinemia and insulin resistance in offspring, as well as an increased body weight that persists into adulthood.


1995 ◽  
Vol 269 (1) ◽  
pp. R30-R37 ◽  
Author(s):  
Z. S. Warwick ◽  
H. P. Weingarten

High-fat diets often promote greater caloric intake and/or weight gain than high-carbohydrate diets in both laboratory animals and humans. Because altering the fat content of a diet simultaneously changes both its sensory properties and postingestive effects, it is unclear whether high-fat hyperphagia is due to the diet's palatability, its postingestive effects, or both. The present studies isolated the independent capacity of the orosensory and postingestive effects of a liquid high-fat diet (High-Fat) to produce overeating relative to an isocaloric liquid high-carbohydrate (High-CHO) diet. Rats fed High-Fat orally ate more calories and gained more weight over 16 days than rats fed High-CHO orally. One-bottle sham-feeding intake of High-Fat and High-CHO did not differ, but in two-bottle sham-feeding tests High-Fat was clearly preferred. When orosensory influences on intake were equated via chronic self-regulated intragastric feeding, High-Fat still promoted greater intake than High-CHO, although absolute intake across both diets was lower during intragastric feeding relative to oral feeding. An analysis of short-term intake revealed that rats accustomed to infusion of High-CHO increased meal size immediately when switched to High-Fat. The present results, coupled with previous findings, suggest that the postingestive effects of fat enhance daily caloric intake in two ways: 1) during a meal, fat produces less suppression of intake per calorie than carbohydrate; and 2) after a meal, fat produces less suppression of intake per calorie during the intermeal interval than carbohydrate.


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