scholarly journals Parental SIRT1 Overexpression Attenuate Metabolic Disorders Due to Maternal High-Fat Feeding

2020 ◽  
Vol 21 (19) ◽  
pp. 7342
Author(s):  
Long T. Nguyen ◽  
Sonia Saad ◽  
Hui Chen ◽  
Carol A. Pollock
Keyword(s):  
Body Weight ◽  
Stress Responses ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
High Fat ◽  
Metabolic Markers ◽  
Lower Body Weight ◽  
Hepatic Glucose ◽  
Fat Feeding

Maternal obesity can contribute to the development of obesity and related metabolic disorders in progeny. Sirtuin (SIRT)1, an essential regulator of metabolism and stress responses, has recently emerged as an important modifying factor of developmental programming. In this study, to elucidate the effects of parental SIRT1 overexpression on offspring mechanism, four experimental groups were included: (1) Chow-fed wild-type (WT)-dam × Chow-fed WT-sire; (2) High-fat diet (HFD)-fed WT-dam × Chow-fed WT-sire; (3) HFD-fed hemizygous SIRT1-transgenic (Tg)-dam × Chow-fed WT-sire; and (4) HFD-fed WT dam × Chow-fed Tg-sire. Our results indicate that Tg breeders had lower body weight and fat mass compared to WT counterparts and gave birth to WT offspring with reductions in body weight, adiposity and hyperlipidaemia compared to those born of WT parents. Maternal SIRT1 overexpression also reversed glucose intolerance, and normalised abnormal fat morphology and the expression of dysregulated lipid metabolism markers, including SIRT1. Despite having persistent hepatic steatosis, offspring born to Tg parents showed an improved balance of hepatic glucose/lipid metabolic markers, as well as reduced levels of inflammatory markers and TGF-β/Smad3 fibrotic signalling. Collectively, the data suggest that parental SIRT1 overexpression can ameliorate adverse metabolic programming effects by maternal obesity.

scholarly journals SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption

2018 ◽  
Vol 315 (2) ◽  
pp. E196-E203 ◽  
Author(s):  
Long The Nguyen ◽  
Hui Chen ◽  
Crystal Mak ◽  
Amgad Zaky ◽  
Carol Pollock ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Liver Damage ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Liver Toxicity ◽  
Sirtuin 1 ◽  
High Fat ◽  
Stress Markers

Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

scholarly journals Evaluation of Anti-Obesity Activity, Acute Toxicity, and Subacute Toxicity of Probiotic Dark Tea

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 99 ◽  
Author(s):  
Wang Ling ◽  
Shungeng Li ◽  
Xingcai Zhang ◽  
Yongquan Xu ◽  
Ying Gao ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
The Body ◽  
High Fat ◽  
Water Group ◽  
Subacute Toxicity ◽  
Infusion Group ◽  
Sd Rats ◽  
Group Ii

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.

Conjugated linoleic acid and chromium lower body weight and visceral fat mass in high-fat-diet-fed mice

Lipids ◽  
2006 ◽  
Vol 41 (5) ◽  
pp. 437-444 ◽  
Author(s):  
Arunabh Bhattacharya ◽  
M. Mizanur Rahman ◽  
Roger McCarter ◽  
Marianne O'Shea ◽  
Gabriel Fernandes
Keyword(s):  
Body Weight ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Fat Mass ◽  
Visceral Fat ◽  
High Fat Diet ◽  
Lower Body ◽  
High Fat ◽  
Lower Body Weight

scholarly journals Changes in Melanocortin Expression and Inflammatory Pathways in Fetal Offspring of Nonhuman Primates Fed a High-Fat Diet

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1622-1632 ◽  
Author(s):  
B. E. Grayson ◽  
P. R. Levasseur ◽  
S. M. Williams ◽  
M. S. Smith ◽  
D. L. Marks ◽  
...  
Keyword(s):  
Adult Female ◽  
Proinflammatory Cytokines ◽  
Stress Responses ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
High Fat ◽  
Melanocortin System ◽  
Third Trimester ◽  
Local Inflammatory Response ◽  
Obesity And Diabetes

The hypothalamic melanocortin system, which controls appetite and energy expenditure, develops during the third trimester in primates. Thus, maternal nutrition and health may have a profound influence on the development of this system. To study the effects of chronic maternal high-fat diet (HFD) on the development of the melanocortin system in the fetal nonhuman primate, we placed adult female macaques on either a control (CTR) diet or a HFD for up to 4 yr. A subgroup of adult female HFD animals was also switched to CTR diet during the fifth year of the study (diet reversal). Third-trimester fetuses from mothers on HFD showed increases in proopiomelanocortin mRNA expression, whereas agouti-related protein mRNA and peptide levels were decreased in comparison with CTR fetuses. Proinflammatory cytokines, including IL-1β and IL-1 type 1 receptor, and markers of activated microglia were elevated in the hypothalamus, suggesting an activation of the local inflammatory response. Fetuses of diet-reversal mothers had normal melanocortin levels. These results raise the concern that chronic consumption of a HFD during pregnancy, independent of maternal obesity and diabetes, can lead to widespread activation of proinflammatory cytokines that may alter the development of the melanocortin system. The abnormalities in the fetal POMC system, if maintained into the postnatal period, could impact several systems, including body weight homeostasis, stress responses, and cardiovascular function. Indeed, the HFD offspring develop early-onset excess weight gain. These abnormalities may be prevented by healthful nutrient consumption during pregnancy even in obese and severely insulin-resistant individuals.

scholarly journals Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition

2021 ◽  
Vol 8 ◽  
Author(s):  
Taida Huang ◽  
Mo Yang ◽  
Yunxin Zeng ◽  
Xiaomin Huang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Metabolic Disorder ◽  
Maternal Smoking ◽  
Metabolic Disorders ◽  
The Body ◽  
Adverse Impact ◽  
Adult Offspring ◽  
High Fat ◽  
Gestation Age

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.

scholarly journals Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

2019 ◽  
Vol 122 (12) ◽  
pp. 1321-1328 ◽  
Author(s):  
Onne A. H. O. Ronda ◽  
Bert J. M. van de Heijning ◽  
Alain de Bruin ◽  
Angelika Jurdzinski ◽  
Folkert Kuipers ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Composition ◽  
High Fat Diet ◽  
Early Life ◽  
Milk Formula ◽  
Continuous Exposure ◽  
Lower Body ◽  
High Fat ◽  
Fat Depots ◽  
Lower Body Weight

AbstractBreast-feeding is associated with a lower risk of developing obesity during childhood and adulthood compared with feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®) programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD) compared with a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breast milk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition and a cIMF, on body weight, glucose homoeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised approximately 50 % milk fat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal day (PN) 16–42 followed by an HFD until PN168. Feeding eIMF v. cIMF in early life resulted in a lower body weight (–9 %) and body fat deposition (–14 %) in adulthood (PN105). The effect appeared transient, as from PN126 onwards, after 12 weeks’ HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27 %) epididymal fat depots and a lower (–26 %) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlie the programming effect observed. Prolonged exposure to an HFD challenge partly overrules the programming effect of early diet.

scholarly journals Long-term consumption of saponins derived from Platycodi radix (22 years old) enhances hepatic insulin sensitivity and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed a high-fat diet

2008 ◽  
Vol 101 (3) ◽  
pp. 358-366 ◽  
Author(s):  
Dae Yeon Kwon ◽  
Young Seob Kim ◽  
Sang Mee Hong ◽  
Sunmin Park
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
High Fat Diet ◽  
Insulin Signalling ◽  
Diabetic Rats ◽  
High Fat ◽  
Platycodi Radix ◽  
Hepatic Glucose ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucose Output

Crude saponins derived from Chinese Platycodi radix have been reported to prevent increases in body weight and liver TAG in mice fed a high-fat diet. We investigated the effects of an extract (PR) taken from Korean Platycodi radix, which is cultivated for 22 years in the ground (Jangsaeng doraji), and its saponins (PRS) on insulin resistance and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed high-fat diets. Four groups were orally supplemented with 2 g PR, 0·2 g PRS, 20 mg rosiglitazone (positive control) or 0·5 g cellulose (negative control) per kg body weight on a daily basis for 8 weeks. We found that PRS lowered body weight, visceral fat mass and serum leptin levels in pancreatectomized rats in comparison to the control. PR enhanced first- and second-phase insulin secretion while PRS stimulated only first-phase insulin secretion. Glucose infusion rates to maintain euglycaemia at hyperinsulinaemic states decreased in a descending order of rosiglitazone, PRS, PR and control, but they increased hepatic glucose output in the same order. This reduction was associated with the storage of decreased TAG and increased glycogen, which was a result of enhanced tyrosine phosphorylation of anti-insulin receptor substrate-2 and serine473 phosphporylation of protein kinase B (PKB, Akt). Improved hepatic insulin signalling led to decreased phosphoenolpyruvate carboxykinase expression and reduced hepatic glucose output accordingly. In conclusion, PRS principally improves glucose homeostasis by enhancing hepatic insulin sensitivity as a consequence of reducing fat storage and stimulating insulin signalling in diabetic rats. In addition, PR contains components that promote glucose-stimulated insulin secretion.

Effects of guanethidine sympathectomy on ventromedial hypothalamic obesity

1983 ◽  
Vol 245 (3) ◽  
pp. R408-R420 ◽  
Author(s):  
T. L. Powley ◽  
M. C. Walgren ◽  
W. B. Laughton
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Salivary Gland ◽  
Food Intake ◽  
High Fat Diet ◽  
Sympathetic Tone ◽  
High Fat ◽  
Hypothalamic Obesity ◽  
Cervical Ganglia ◽  
Fat Feeding

Since ventromedial hypothalamic (VMH) lesions apparently produce chronic increases in parasympathetic activity and decreases in sympathetic responses, two experiments were performed to determine whether decreases in sympathetic tone alone are sufficient either to produce elements of the VMH syndrome or to potentiate the expression of the syndrome in animals with lesions. In experiment 1, rats that had been injected with guanethidine sulfate for 5 wk (40 mg X kg-1 X day-1) to produce a permanent sympathectomy (SympX) were maintained on a high-fat diet and subsequently subjected to VMH lesions. In experiment 2, adrenal-demedullated animals were treated with guanethidine for 6 wk and then subsequently underwent VMH lesions. SympX in the studies (81 and 85% depletion of superior cervical ganglia neurons, respectively) did duplicate the effects of VMH lesions on salivary gland weights. In neither experiment, however, did SympX alone or in combination with demedullation mimic the effects of VMH lesions on food intake, body weight, or body fat. Determinations of free fatty acids (FFAs) in the experiments confirmed that VMH lesions elevate basal FFA levels, but they also indicated that effective VMH lesions need not impair the FFA mobilization to 2-deoxyglucose challenges as some basomedial hypothalamic lesions do. In addition, experiment 2, which employed a prolonged period of high-fat feeding, revealed that SympX plus adrenal demedullation could potentiate (a 13% increase) the effects of VMH lesions on body weight. The results taken together do not support the conclusion that a preponderance of the VMH syndrome can be accounted for by the type of reduction in sympathetic tone produced by guanethidine.

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