scholarly journals Gestational obesity accentuates obesity in obesity-prone progeny

1998 ◽  
Vol 275 (4) ◽  
pp. R1374-R1379 ◽  
Author(s):  
Barry E. Levin ◽  
Elizabeth Govek
Keyword(s):  
Genetic Background ◽  
Maternal Obesity ◽  
High Energy ◽  
Liquid Diet ◽  
The Other ◽  
Glucose Levels ◽  
Fat Depots ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Fat Pads

Maternal obesity and genetic background can affect the development of obesity and diabetes in offspring. Here we used selected strains of rats resistant (DR) vs. susceptible to development of diet-induced obesity (DIO) on high-energy (HE) diets to assess this issue. DR and DIO dams were fed either Chow or HE diet for 4 wk. DIO HE diet-fed dams and additional DR rats fed a palatable liquid diet (Ensure) became more obese and hyperinsulinemic than the other groups. During lactation, all dams were fed their respective diets, and offspring were fed Chow from weaning to 16 wk of age. All offspring of DIO dams gained more weight and had heavier retroperitoneal fat pads and higher leptin levels than DR progeny, but offspring of the more obese DIO HE dams had heavier fat pads and higher glucose levels than DIO Chow offspring. After 4 wk on HE diet, all DIO offspring gained more weight and had heavier total adipose depots and higher insulin and leptin levels than DR offspring. Offspring of DIO HE dams also gained more weight and had heavier fat depots and higher leptin levels than DIO Chow offspring. Therefore maternal obesity and hyperinsulinemia were associated with increased obesity in those offspring already genetically predisposed to become obese.

LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice

2002 ◽  
Vol 282 (1) ◽  
pp. E207-E214 ◽  
Author(s):  
Sandra A. Schreyer ◽  
Cynthia Vick ◽  
Theodore C. Lystig ◽  
Paul Mystkowski ◽  
Renée C. LeBoeuf
Keyword(s):  
Apolipoprotein E ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Wild Type ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Glucose And Lipid Homeostasis

The aim of this study was to determine whether phenotypes associated with type 2 diabetes are altered in dyslipidemic obese mice. C57BL/6 wild-type, low-density lipoprotein (LDL) receptor-deficient (LDLR−/−), and apolipoprotein E-deficient (apoE−/−) mice were fed a high-fat, high-carbohydrate diet (diabetogenic diet), and the development of obesity, diabetes, and hypertriglyceridemia was examined. Wild-type mice became obese and developed hyperglycemia, but not hypertriglyceridemia, in response to this diet. LDLR−/− mice fed the diabetogenic diet became more obese than wild-type mice and developed severe hypertriglyceridemia and hyperleptinemia. Surprisingly, glucose levels were only modestly higher and insulin levels and insulin-to-glucose ratios were not strikingly different from those of wild-type mice. In contrast, diabetogenic diet-fed apoE−/− mice were resistant to changes in glucose and lipid homeostasis despite becoming obese. These data suggest that modifications in lipoprotein profiles associated with loss of the LDL receptor or apoE function have profound and unique consequences on susceptibility to diet-induced obesity and type 2 diabetic phenotypes.

scholarly journals Dietary Alleviation of Maternal Obesity and Diabetes: Increased Resistance to Diet-Induced Obesity Transcriptional and Epigenetic Signatures

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66816 ◽  
Author(s):  
Linda Attig ◽  
Alexandre Vigé ◽  
Anne Gabory ◽  
Moshen Karimi ◽  
Aurore Beauger ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Epigenetic Signatures

Initiation and perpetuation of obesity and obesity resistance in rats

1989 ◽  
Vol 256 (3) ◽  
pp. R766-R771 ◽  
Author(s):  
B. E. Levin ◽  
S. Hogan ◽  
A. C. Sullivan
Keyword(s):  
High Energy ◽  
The Body ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Fat Pads

A search was made for predisposing factors and sequelae of diet-induced obesity (DIO) or resistance to DIO (DR). During 3 mo on a high-energy (CM) diet, two-thirds of the male Sprague-Dawley rats ate 16% more calories over the first 30 days and developed DIO. The remaining one-third were DR, gaining the same amount of weight as chow-fed controls. Basal and norepinephrine (NE)-stimulated in vivo O2 consumption, performed before rats were placed on the CM diet, was the same in those rats that later became DR or DIO after 3 mo on the CM diet. DR rats were 4% lighter, whereas DIO rats were equal to chow-fed rats before their exposure to the CM diet. When CM-fed rats were switched to chow, DIO rats took 14 wk to reduce their body and retroperitoneal fat pad weights to those of chow-fed controls, whereas DR rats gained only 40% of the body weight, and fat pads were 34% lighter than controls. After 14 wk, DIO rats were neither hyperinsulinemic nor insulin resistant, whereas DR rats had 64% reduced areas under their insulin curves after intravenous glucose (1 g/kg) compared with controls. Unlike younger rats, animals here had inconsistent plasma NE responses to intravenous glucose. Therefore the CM diet produces DR and DIO states that tend to become self-perpetuating once established.

Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1

2010 ◽  
Vol 298 (3) ◽  
pp. G419-G424 ◽  
Author(s):  
Quan Shang ◽  
Monica Saumoy ◽  
Jens Juul Holst ◽  
Gerald Salen ◽  
Guorong Xu
Keyword(s):  
Insulin Resistance ◽  
Bile Acid ◽  
Rat Model ◽  
Plasma Glucose ◽  
Receptor Activation ◽  
High Energy ◽  
Farnesoid X Receptor ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Diet Induced Obesity

Bile acid sequestrants have been shown to lower glucose levels in patients with type 2 diabetes. To investigate how colesevelam (CL) HCl improves hyperglycemia, studies were conducted in diet-induced obesity (F-DIO) rats, which develop insulin resistance when fed a high-energy (high fat/high sucrose) diet (HE). The rats were fed HE; HE + 2% CL; HE + 0.02% SC-435 (SC), an apical sodium-dependent bile acid transporter inhibitor; and regular chow (controls). After 4 wk of treatment, both in the HE group and the SC + HE group, plasma glucose and insulin levels remained elevated compared with baseline values throughout an oral glucose tolerance test (OGTT). In contrast, in the CL + HE group, plasma glucose levels returned to baseline by the end of the test, and insulin peaked in 15–30 min and then returned to baseline. CL induced release of glucagon-like peptide-1 (GLP-1) because the area under the curve of plasma total GLP-1 in the CL + HE group was significantly greater than in the HE group during the OGTT. Bile acid concentrations in the portal blood did not decrease in the HE group but declined significantly both in the CL + HE and SC + HE groups with reduced farnesoid X receptor activation compared with controls. We concluded that CL reduces plasma glucose levels by improving insulin resistance in this rat model. It is unlikely that the improvement is attributable to decreased bile acid flux to the liver but is likely secondary to induced GLP-1 secretion, which improves insulin release.

Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia

2004 ◽  
Vol 287 (5) ◽  
pp. R1110-R1115 ◽  
Author(s):  
Nancy C. Tkacs ◽  
Barry E. Levin
Keyword(s):  
Weight Gain ◽  
Arcuate Nucleus ◽  
Body Weight Gain ◽  
Inverse Correlation ◽  
High Energy ◽  
Lower Plasma ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Altered Glucose

Rats that develop diet-induced obesity (DIO) on a 31% fat [high-energy (HE)] diet have defective sensing and responding to altered glucose levels compared with diet-resistant (DR) rats. Thus we postulated that they would also have defective counterregulatory responses (CRR) to insulin-induced hypoglycemia (IIH). Chow-fed selectively bred DIO and DR rats underwent three sequential 60-min bouts of IIH separated by 48 h. Glucose levels fell comparably, but DIO rats had 22–29% lower plasma epinephrine (Epi) levels during the first two bouts than DR rats. By the third trial, despite comparable Epi levels, DIO rats had lower 30-min glucose levels and rebounded less than DR rats 85 min after intravenous glucose. Although DIO rats gained more carcass and fat weight after 4 wk on an HE diet than DR rats, they were unaffected by prior IIH. Compared with controls, DR rats with prior IIH and HE diet had higher arcuate nucleus neuropeptide Y (50%) and proopiomelanocortin (POMC; 37%) mRNA and an inverse correlation ( r = 0.85; P = 0.004) between POMC expression and body weight gain on the HE diet. These data suggest that DIO rats have a preexisting defect in their CRR to IIH but that IIH does not affect the expression of their hypothalamic neuropeptides or weight gain as it does in DR rats.

VARIATIONS IN THE BLOOD COMPOSITION OF NON-PREGNANT HEREFORD AND ANGUS HEIFERS FED INDIVIDUALLY IN CONFINEMENT ON TWO LEVELS OF ENERGY INTAKE

1979 ◽  
Vol 59 (4) ◽  
pp. 663-674
Author(s):  
D. M. BOWDEN ◽  
G. C. KOZUB
Keyword(s):  
Energy Intake ◽  
High Energy ◽  
The Other ◽  
Nonesterified Fatty Acid ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Blood Constituents ◽  
Glucose Levels ◽  
Dietary Phosphorus ◽  
Angus Heifers

Ten Hereford heifers and 10 Angus heifers were given a high energy diet and equal numbers of Hereford and Angus heifers a low energy diet in individual pens from an average age of 476 day s. After 140 day s, one-half of the heifers of each breed on each energy level were changed to the other level while the other half of the heifers remained on the same level for a further 140 days. Blood samples were taken each 28 days to determine the influence of date of sampling and energy intake on levels of organic and inorganic constituents in the blood. Daily gains averaged 0.2 kg on the low and 0.6 kg on the high energy intake. Levels of all the blood constituents measured differed significantly (P < 0.05) between some of the sampling days. Levels of packed cell volume, whole blood glucose and corrected glucose were highest in January, which was the coldest day of blood sampling, and remained high until April. Serum potassium levels declined over the period of the trial. Total serum cholesterol levels increased (P < 0.01) and plasma nonesterified fatty acid levels decreased (P < 0.05) when energy intakes were increased. Serum phosphorus levels increased (P < 0.05) when dietary phosphorus intakes increased. Angus heifers had higher (P < 0.05) corrected glucose levels in their blood than did Hereford heifers.

scholarly journals Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

2009 ◽  
Vol 296 (3) ◽  
pp. R521-R527 ◽  
Author(s):  
Boman G. Irani ◽  
Christelle Le Foll ◽  
Ambrose A. Dunn-Meynell ◽  
Barry E. Levin
Keyword(s):  
Calcium Imaging ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
High Energy ◽  
Hypothalamic Nucleus ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Diet Intake ◽  
Induced Changes

Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Only DIO dams became obese on HE diet when they and DR dams were fed 5% fat chow or HE diets throughout gestation and lactation. Leptin sensitivity of dissociated arcuate (ARC) and ventromedial (VMN) hypothalamic nucleus neurons from the 3- to 4-wk-old offspring was assessed using fura-2 calcium imaging to monitor leptin-induced changes in intracellular calcium ([Ca2+]i) as an index of neuronal activity. At 0.1, 1, 10 fmol/l leptin, ∼4 times more VMN and ARC neurons were excited than inhibited by leptin. In the VMN, leptin excited up to 41% fewer neurons, and these excited neurons were less sensitive to increasing doses of leptin in DIO compared with DR offspring. Also, maternal HE diet intake decreased the percentage of leptin-excited VMN neurons in both DIO and DR offspring and decreased the percentage of leptin-inhibited VMN neurons by 36% only in DIO offspring. In the ARC, there were no genotype or maternal diet effects on the percentage of ARC neurons excited by leptin. However, those DR neurons that were leptin excited were more sensitive to leptin than were those from DIO offspring. These data suggest that reduced responsiveness of DIO VMN neurons to leptin's excitatory effects may be an important contributing factor to the reduced anorectic and thermogenic leptin responsiveness of DIO rats in vivo.

scholarly journals Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons

2009 ◽  
Vol 297 (5) ◽  
pp. R1351-R1357 ◽  
Author(s):  
Christelle Le Foll ◽  
Boman G. Irani ◽  
Christophe Magnan ◽  
Ambrose Dunn-Meynell ◽  
Barry E. Levin
Keyword(s):  
Maternal Obesity ◽  
High Energy ◽  
Hypothalamic Nucleus ◽  
Long Chain Fatty Acids ◽  
Diet Induced Obesity ◽  
Ventromedial Hypothalamic Nucleus ◽  
Maternal Genotype ◽  
Dietary Content ◽  
Diet Intake ◽  
High Sucrose

Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high-sucrose, high-energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Also, only DIO dams become obese when they and DR dams are fed HE diet throughout gestation and lactation. We assessed glucose and oleic acid (OA) sensitivity of dissociated ventromedial hypothalamic nucleus (VMN) neurons from 3- to 4-wk old offspring of DIO and DR dams fed chow or HE diet using fura-2 calcium imaging to monitor intracellular calcium fluctuations as an index of neuronal activity. Offspring of DIO dams fed chow had ∼2-fold more glucose-inhibited (GI) neurons than did DR offspring. This difference was eliminated in offspring of DIO dams fed HE diet. At 2.5 mM glucose, offspring of chow-fed DIO dams had more GI neurons that were either excited or inhibited by OA than did DR offspring. Maternal HE diet intake generally increased the percentage of neurons that were excited and decreased the percentage that were inhibited by OA in both DIO and DR offspring. However, this effect was more pronounced in DIO offspring. These data, as well as concentration-dependent differences in OA sensitivity, suggest that genotype, maternal obesity, and dietary content can all affect the sensitivity of offspring VMN neurons to glucose and long-chain fatty acids. Such altered sensitivities may underlie the propensity of DIO offspring to become obese when fed high-fat, high-sucrose diets.

150 EFFECT OF MATERNAL OBESITY ON PERICONCEPTION FERTILITY AND BLASTOCYST GENE EXPRESSION IN THE MOUSE MODEL

2012 ◽  
Vol 24 (1) ◽  
pp. 187
Author(s):  
P. Bermejo-Alvarez ◽  
C. S. Rosenfeld ◽  
R. M. Roberts
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Embryo Development ◽  
Maternal Obesity ◽  
Control Diet ◽  
Ovulation Rate ◽  
The Other ◽  
Protective Mechanism ◽  
Metabolism Regulation ◽  
Diet Induced Obesity

Obesity is frequently associated with infertility in humans and domestic animals. In this study, we aimed to study the effect of diet-induced obesity on oestrus cyclicity, ovulation rate, pre-implantation embryo development and blastocysts gene expression. Twenty-one NIH Swiss female mice were divided in 2 groups: one fed with a control diet (C, n = 9) and the other with a diet high in fat (F, n = 12) for 12 weeks. Dams were naturally bred and killed 3.5 days post-coitum. Bodyweight, numbers of corpora lutea and embryos and days required to breed the dams were recorded. Blastocysts were recovered and snap frozen in groups representing the individual dams. Expression of 10 candidate genes was analysed relative to H2afz. Data (means ± standard error of the means) were analysed by ANOVA (P < 0.05, significant). Five mice in the F group failed to breed during 20 days. These acyclic animals were significantly heavier than the other 7 of the F group (53.8 ± 3.8 vs 41.6 ± 0.9 g), with 4 weighting over 50 g. The seven cyclic animals in the F group showed a higher weight (41.6 ± 0.9 vs 31 ± 0.8 g) and higher number of days to mate (7.3 ± 1.6 vs 2.9 ± 0.5) compared with group C, but ovulation rates did not differ and reflected final blastocyst recovery. The expression level of 5 genes (Insr, Igf1r, Igf2r, Adipor1 and Adipor2) encoding for receptors of hormones related to metabolism regulation did not differ among groups. Two genes with roles in glucose (Scl2a1) and lipid transport (Ldlr) were down-regulated in the F group compared with the C group (Scl2a1: 1 ± 0.1 vs 1.38 ± 0.1; Ldlr: 1 ± 0.1 vs 1.24 ± 0.1); however, there were no differences in expression of the genes Gapdh (which encodes an essential glycolytic enzyme), Cpt1a (whose product catalyzes the rate limiting step of β-oxidation) and Sod2 (which encodes the mitochondrial isoform of superoxide dismutase). These results suggest that diet-induced obesity in the mouse model reduces fertility through oestrus cyclicity, blocking or prolonging the oestrus cycle, but there was no effect on ovulation rate or embryo development in those females that ovulated. The down-regulation of 2 genes related to nutrient uptake (Slc2a1 and Ldlr) in the F group suggests a protective mechanism to abate the excess of nutrients. Such protection may be effective, as the expression of genes for key metabolic markers for anaerobic glycolysis, fatty acid metabolism and oxidative stress remained unaltered. Supported by Lalor Foundation to P. Bermejo-Alvarez, HD21896 to R. M. Roberts and RC1 ES018195 to C. S. Rosenfeld.

Defective glucoregulation of brain alpha 2-adrenoceptors in obesity-prone rats

1993 ◽  
Vol 264 (2) ◽  
pp. R305-R311 ◽  
Author(s):  
B. E. Levin ◽  
B. Planas
Keyword(s):  
Plasma Glucose ◽  
High Energy ◽  
Hypothalamic Nucleus ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Low Glucose ◽  
Positive Correlations

Only half the male Sprague-Dawley rats fed high-energy diets develop diet-induced obesity (DIO); the rest are diet resistant (DR). It has been established that rats prone to develop DIO have decreased basal brain alpha 2-adrenoceptor levels compared with DR-prone rats and that DIO- but not DR-prone rats show glucose-induced increases in plasma norepinephrine (NE) levels. Because it has also been shown that alpha 2-adrenoceptors modulate ingestive and autonomic functions and are responsive to changes in plasma glucose levels, we tested the hypothesis that DIO- and DR-prone rats would regulate these receptors differently by using hyperinsulinemic clamping to vary plasma glucose levels. Rats with low glucose-induced plasma NE responses (DR-prone) showed significant positive correlations (r = 0.724-0.919) between plasma glucose levels and alpha 2-adrenoceptor ([3H]paraminoclonidine) binding in 5 of 17 brain areas (anterior, ventromedial, and arcuate hypothalamic nucleus; medial and basomedial amygdalar nucleus) assessed by autoradiographic techniques. Near-significant correlations were also seen in the paraventricular nucleus and lateral hypothalamus. High glucose-induced NE responders (DIO-prone) showed such a correlation only in the arcuate nucleus (r = 0.726). There was little glucoregulation of alpha 1-adrenoceptors. The defective ability of DIO-prone rats to alter brain alpha 2-adrenoceptors to changes in plasma glucose levels might underlie their predisposition to become obese on diets high in sucrose.

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