Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance

Abstract Objectives Pregnancy is associated with physiological alterations in insulin sensitivity and lipid metabolism. This study investigates the associations between pregestational body mass index (pBMI) and the rate of gestational weight gain (rGWG) in the second trimester with the biomarkers of lipid, fatty acids metabolism and insulin resistance. Methods Sixty nine pregnant women followed. The body weights of the pregnant women were measured and blood samples were obtained at 11–14th and 24–28th weeks of pregnancy. Glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, insulin levels and fatty acids were measured. Rate of GWG (kg/week) and The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were calculated. The pregnant women were stratified according to their pBMI and the 2nd trimester rGWG. Results The rate of GWG was significantly higher for the group with pBMI<25, compared to the group with pBMI≥25 (p=0.024). Triglyceride, total cholesterol, LDL and HDL cholesterol were significantly increased in the second trimester compared with the first trimester. Palmitic acid, oleic acid, linoleic acid, myristic acid, docosahexaenoic acid (DHA), arachidonic acid (AA), total omega-6 (n − 6) and omega-3 (n − 3) fatty acid levels and n − 6/n − 3 ratio were significantly higher in the second trimester. Glucose was significantly decreased and insulin was increased in the second trimester. In the overweight/obese group; HOMA-IR, insulin, AA, palmitoleic acid and stearic acid were found to be high in comparison to the group with low/normal pBMI. No parameters were associated with rGWG. Conclusions The changes in lipid parameters, free fatty acids, insulin and HOMA-IR in the second trimester were compatible with the changes in lipid metabolism and the development of insulin resistance. Pregestational BMI was shown to have a stronger influence on lipid profile, insulin resistance, and fatty acids than rGWG.

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Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters

Annals of Neurosciences ◽

10.1177/09727531211005738 ◽

2021 ◽

pp. 097275312110057

Author(s):

Archana Gaur ◽

G.K. Pal ◽

Pravati Pal

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Food Intake ◽

Ventromedial Hypothalamus ◽

Female Rats ◽

Metabolic Parameters ◽

Male Rats ◽

Significant Weight Gain ◽

The Metabolic Syndrome

Background: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. Purpose: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. Methods: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. Results: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. Conclusion: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

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Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis

The Lancet ◽

10.1016/s0140-6736(04)17663-0 ◽

2005 ◽

Vol 365 (9453) ◽

pp. 36-42 ◽

Cited By ~ 785

Author(s):

Mark A Pereira ◽

Alex I Kartashov ◽

Cara B Ebbeling ◽

Linda Van Horn ◽

Martha L Slattery ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Fast Food ◽

Food Habits ◽

Prospective Analysis

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The prophylactic potential of Zingiber officinale flowers and leaves extract to mitigate hyperglycemia in Sprague Dawley rats

Nutrition & Food Science ◽

10.1108/nfs-02-2021-0069 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Saira Tanweer ◽

Tariq Mehmood ◽

Saadia Zainab ◽

Zulfiqar Ahmad ◽

Muhammad Ammar Khan ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

Zingiber Officinale ◽

Sprague Dawley ◽

Content Type ◽

Sprague Dawley Rats ◽

Hematological Analysis ◽

Therapeutic Tools

Purpose Innovative health-promoting approaches of the era have verified phytoceutics as one of the prime therapeutic tools to alleviate numerous health-related ailments. The purpose of this paper is to probe the nutraceutic potential of ginger flowers and leaves against hyperglycemia. Design/methodology/approach The aqueous extracts of ginger flowers and leaves were observed on Sprague Dawley rats for 8 weeks. Two parallel studies were carried out based on dietary regimes: control and hyperglycemic diets. At the end of the experimental modus, the overnight fed rats were killed to determine the concentration of glucose and insulin in serum. The insulin resistance and insulin secretions were also calculated by formulae by considering fasting glucose and fasting insulin concentrations. Furthermore, the feed and drink intakes, body weight gain and hematological analysis were also carried out. Findings In streptozotocin-induced hyperglycemic rats, the ginger flowers extract depicted 5.62% reduction; however, ginger leaves extract reduced the glucose concentration up to 7.11% (p = 0.001). Similarly, ginger flowers extract uplifted the insulin concentration up to 3.07%, while, by ginger leaves extract, the insulin value increased to 4.11% (p = 0.002). For the insulin resistance, the ginger flower showed 5.32% decrease; however, the insulin resistance was reduced to 6.48% by ginger leaves (p = 0.014). Moreover, the insulin secretion increased to 18.9% by flower extract and 21.8% by ginger leave extract (p = 0.001). The feed intake and body weight gain increased momentously by the addition of ginger flowers and leaves; however, the drink intake and hematological analysis remained non-significant by the addition of ginger parts. Originality/value Conclusively, it was revealed that leaves have more hypoglycemic potential as compared to flowers.

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Abstract P250: Insulin Resistance During Pregnancy is Inversely Associated With Gynoid Fat Distribution Postpartum

Circulation ◽

10.1161/circ.137.suppl_1.p250 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Katherine H Ingram ◽

Roxanna Lopez

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Insulin Sensitivity ◽

Gestational Weight Gain ◽

Body Fat ◽

Visceral Fat ◽

Post Partum ◽

Lower Body ◽

Negatively Associated ◽

Gestational Weight

An association between abdominal adiposity and insulin resistance is well-established. Recent research indicates that subcutaneous fat accumulation in the lower body may be associated with higher levels of insulin sensitivity. Hypothesis: This pilot study tested the hypothesis that the distribution of body fat in the lower body after pregnancy is negatively associated with gestational insulin resistance. Methods: In 32 nulliparous pregnant women (age 27±4.5, BMI 29.5±7.9, 69% non-hispanic white), the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed from fasting glucose and insulin at 24-28 weeks gestation. Body composition was assessed at mid-gestation (18-20 weeks) and at four weeks post-partum. Total body fat was estimated via bioelectrical impedance (InBody 720) and skinfold thicknesses were measured at seven sites. Dual-energy xray absorptiometry (DXA) measures of regional fat (gynoid, visceral, and leg) were obtained post-partum only. Gestational weight gain was monitored by medical records. Partial correlation analyses were controlled for age and race and then analyses were repeated controlling for baseline (mid-gestation) body fat percent. HOMA-IR was log-transformed for normality. Results: HOMA-IR was associated with post-partum body fat ( r =0.45, p < .05) and adiposity in the trunk region ( r =0.58, 0.57 and 0.52 for DXA visceral fat, suprailiac skinfold, and abdominal skinfold, respectively, p < .01), but not with gestational weight gain ( r =.07, p = ns), DXA gynoid region ( r = 0.26, p = ns), or any other leg measure. When analyses were further controlled for baseline body fat, post-partum measures of lower-body adiposity were strongly and negatively correlated with HOMA-IR ( r = -0.66, -0.48, and -0.48 for thigh skinfold, DXA gynoid, and DXA leg, respectively, p < .05 for all). Neither DXA visceral fat ( r = .23; p = ns) nor any other post-partum fat measures were associated with HOMA-IR when controlling for baseline body fat. Conclusions: Gestational insulin resistance was negatively associated with post-partum thigh fat accumulation, independent of overall body fat. These data indicate that insulin sensitivity may be associated with the ability to store fat in the lower body and should warrant further study of subcutaneous leg fat as a metabolically “healthy” storage depot.

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Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis

Nutrients ◽

10.3390/nu10111568 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1568 ◽

Cited By ~ 9

Author(s):

David Simmons ◽

Roland Devlieger ◽

Andre van Assche ◽

Sander Galjaard ◽

Rosa Corcoy ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Gestational Diabetes ◽

Gestational Weight Gain ◽

First Trimester ◽

Obstetric Outcomes ◽

Lifestyle Interventions ◽

Gestational Weight ◽

Randomized Controlled ◽

Post Hoc

Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m2 <20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24–28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35–37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester.

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Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽

10.1210/en.2015-1159 ◽

2015 ◽

Vol 156 (11) ◽

pp. 4071-4080 ◽

Cited By ~ 17

Author(s):

Amanda Hurliman ◽

Jennifer Keller Brown ◽

Nicole Maille ◽

Maurizio Mandala ◽

Peter Casson ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Endothelial Dysfunction ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Polycystic Ovary ◽

Phase 1 ◽

Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

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PS20 - 95. Antipsychotic drug induced weight gain and insulin resistance: personality as a risk factor

Nederlands Tijdschrift voor Diabetologie ◽

10.1007/s12467-012-0129-5 ◽

2012 ◽

Vol 10 (3) ◽

pp. 166-167

Author(s):

Simon Evers ◽

Marianne Adema ◽

Jacolien Graver ◽

Gertjan van Dijk ◽

Anton Scheurink

Keyword(s):

Insulin Resistance ◽

Risk Factor ◽

Weight Gain ◽

Antipsychotic Drug ◽

Drug Induced

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Estrogen Replacement Reverses Olanzapine-Induced Weight Gain and Hepatic Insulin Resistance in Ovariectomized Diabetic Rats

Neuropsychobiology ◽

10.1159/000285780 ◽

2010 ◽

Vol 61 (3) ◽

pp. 148-161 ◽

Cited By ~ 15

Author(s):

Sunmin Park ◽

Sang Mee Hong ◽

I.L. Sung Ahn ◽

Da Sol Kim ◽

Sung Hoon Kim

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Diabetic Rats ◽

Hepatic Insulin Resistance ◽

Estrogen Replacement

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The consequences of obesity and excess weight gain in pregnancy

Proceedings of The Nutrition Society ◽

10.1017/s0029665111003077 ◽

2011 ◽

Vol 70 (4) ◽

pp. 450-456 ◽

Cited By ~ 81

Author(s):

Jane E. Norman ◽

Rebecca Reynolds

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Gestational Diabetes ◽

Pregnant Women ◽

Postpartum Haemorrhage ◽

Maternal Obesity ◽

Adverse Pregnancy Outcome ◽

Operative Delivery ◽

Adverse Pregnancy ◽

In Pregnancy

The prevalence of obesity in pregnancy is rising exponentially; about 15–20% of pregnant women now enter pregnancy with a BMI which would define them as obese. This paper provides a review of the strong links between obesity and adverse pregnancy outcome which operate across a range of pregnancy complications. For example, obesity is associated with an increased risk of maternal mortality, gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum haemorrhage. Obesity also complicates operative delivery; it makes operative delivery more difficult, increases complications and paradoxically increases the need for operative delivery. The risk of the majority of these complications is amplified by excess weight gain in pregnancy and increases in proportion to the degree of obesity, for example, women with extreme obesity have OR of 7·89 for gestational diabetes and 3·84 for postpartum haemorrhage compared to their lean counterparts. The consequences of maternal obesity do not stop once the baby is born. Maternal obesity programmes a variety of long-term adverse outcomes, including obesity in the offspring at adulthood. Such an effect is mediated at least in part via high birthweight; a recent study has suggested that the odds of adult obesity are two-fold greater in babies weighing more than 4 kg at birth. The mechanism by which obesity causes adverse pregnancy outcome is uncertain. This paper reviews the emerging evidence that hyperglycaemia and insulin resistance may both play a role: the links between hyperglycaemia in pregnancy and both increased birthweight and insulin resistance have been demonstrated in two large studies. Lastly, we discuss the nature and rationale for possible intervention strategies in obese pregnant women.

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