Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPARγ Mutant Rats

Pulsed antibiotic treatment (PAT) early in life increases risk of obesity. Prebiotics can reduce fat mass and improve metabolic health. We examined if co-administering prebiotic with PAT reduces obesity risk in rat pups weaned onto a high fat/sucrose diet. Pups were randomized to (1) control [CTR], (2) antibiotic [ABT] (azithromycin), (3) prebiotic [PRE] (10% oligofructose (OFS)), (4) antibiotic + prebiotic [ABT + PRE]. Pulses of antibiotics/prebiotics were administered at d19–21, d28–30 and d37–39. Male and female rats given antibiotics (ABT) had higher body weight than all other groups at 10 wk of age. The PAT phenotype was stronger in ABT males than females, where increased fat mass, hyperinsulinemia and insulin resistance were present and all reversible with prebiotics. Reduced hypothalamic and hepatic expression of insulin receptor substrates and ileal tight junction proteins was seen in males only, explaining their greater insulin resistance. In females, insulin resistance was improved with prebiotics and normalized to lean control. ABT reduced Lactobacillaceae and increased Bacteroidaceae in both sexes. Using a therapeutic dose of an antibiotic commonly used for acute infection in children, PAT increased body weight and impaired insulin production and insulin sensitivity. The effects were reversed with prebiotic co-administration in a sex-specific manner.

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Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: a randomized study

Acta Endocrinologica ◽

10.1530/eje.1.02065 ◽

2006 ◽

Vol 154 (1) ◽

pp. 131-139 ◽

Cited By ~ 18

Author(s):

Lenora M Camarate S M Leão ◽

Mônica Peres C Duarte ◽

Dalva Margareth B Silva ◽

Paulo Roberto V Bahia ◽

Cláudia Medina Coeli ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Blood Pressure ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Postmenopausal Women ◽

Fat Mass ◽

Visceral Fat ◽

Increased Risk

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42–62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.

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Association of Plasma Levels of Resistin with Subcutaneous Fat Mass and Markers of Inflammation but not with Metabolic Determinants or Insulin Resistance

Journal of Korean Medical Science ◽

10.3346/jkms.2009.24.4.695 ◽

2009 ◽

Vol 24 (4) ◽

pp. 695 ◽

Cited By ~ 15

Author(s):

Jong Chul Won ◽

Cheol-Young Park ◽

Won Young Lee ◽

Eon Sook Lee ◽

Sang Woo Oh ◽

...

Keyword(s):

Insulin Resistance ◽

Fat Mass ◽

Plasma Levels ◽

Subcutaneous Fat ◽

Markers Of Inflammation

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Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

International Journal of Molecular Sciences ◽

10.3390/ijms19103281 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3281 ◽

Cited By ~ 4

Author(s):

Youngmi Lee ◽

Eun-Young Kwon ◽

Myung-Sook Choi

Keyword(s):

Insulin Resistance ◽

Energy Expenditure ◽

Body Fat ◽

Fat Mass ◽

High Fat Diet ◽

Plasma Cholesterol ◽

Cellular Respiration ◽

Body Fat Mass ◽

High Fat ◽

Diet Induced Obesity

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

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Consumption of added sugars and development of metabolic syndrome components among a sample of youth at risk of obesity

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0456 ◽

2014 ◽

Vol 39 (4) ◽

pp. 512-512 ◽

Cited By ~ 12

Author(s):

JiaWei Wang

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Glucose Tolerance ◽

Fat Mass ◽

Diet Quality ◽

Healthy Eating Index ◽

Added Sugar ◽

Added Sugars ◽

Sugar Intake

Previous evidence showed controversial links between added sugar intake, diet quality, and increasing prevalence of metabolic syndrome (MetS) components (abdominal adiposity, dysglycemia, elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C), and hypertriglyceridemia) in youth, and most studied only its liquid source of sugar-sweetened beverages (SSB). To better understand the extent of the detrimental effects of added sugars from both liquid and solid sources to diets in terms of nutrient and food intake and metabolic consequences in children, 3 studies were undertaken to (i) quantify the associations of added sugar intake with overall diet quality and adiposity indicators; (ii) assess whether excess weight and glucose tolerance status modifies the associations between consumption of added sugars and MetS components; and (iii) evaluate whether consumption of added sugars predicts the development of MetS components over time. Data for these studies were obtained from the Quebec Adiposity and Lifestyle Investigation in Youth cohort. Caucasian children (8 to 10 years at baseline, N = 630) with at least 1 obese biological parent were recruited from 1040 Quebec primary schools and followed-up 2 years later (N = 564). Dietary intake, including added sugars (liquid vs. solid) and Canadian Healthy Eating Index (HEI-C) was assessed in three 24-h recalls at baseline. Adiposity indicators included measured height and weight for body mass index (BMI), BMI z score, waist circumference (WC), and fat mass (by dual-energy X-ray absorptiometry). Plasma glucose and insulin were measured at fasting and by oral glucose tolerance tests to calculate the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda IS index (Matsuda-ISI). Systolic blood pressure (SBP), concentration of triglycerides and HDL-C were measured by standard instruments. Multivariate linear regression models were used, adjusting for age, sex, pubertal status (by Tanner stage), energy intake, fat mass, and physical activity (by 7-day accelerometer). The main findings include the following: (i) Higher consumption of added sugars from SSB or solid sources was associated with lower nutrient density and lower HEI-C. Positive associations with adiposity indicators were observed with consumption of added sugars from liquid sources only. (ii) Higher SSB consumption was associated with higher HOMA-IR and higher SBP among overweight children (≥85th BMI percentile), as well as higher SBP and higher WC among children with impaired glucose tolerance. These associations with metabolic indicators were not observed among children whose BMI was below 85th percentile. (iii) No association with added sugar intake was observed for 2-year changes in adiposity, but higher consumption of added sugars from liquid sources was associated with higher fasting glucose, higher fasting insulin, higher HOMA-IR, and lower Matsuda-ISI. In conclusion, this thesis suggested that consumption of added sugars from both solid and liquid sources was associated with a lower overall diet quality, but only added sugars from liquid sources was associated with adiposity indicators. Cross-sectional links with higher levels of SSB intake and MetS components were more evident among overweight/obese and glucose-intolerant children. Consumption of added sugars from liquid sources was not associated with changes in adiposity over 2 years, but was clearly associated with development of impaired glucose homeostasis and insulin resistance. This thesis presents further evidence on the nutritional and metabolic consequences of consuming added sugar from liquid and solid sources.

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Omentin-1 Changes following Biliopancreatic Diversion and Relationship with Cardiovascular Risk Factors

Annals of Nutrition and Metabolism ◽

10.1159/000491434 ◽

2018 ◽

Vol 73 (2) ◽

pp. 106-112 ◽

Cited By ~ 2

Author(s):

Daniel Antonio de Luis ◽

Susana García Calvo ◽

Juan Jose Lopez Gomez ◽

Olatz Izaola ◽

David Primo ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Bariatric Surgery ◽

Weight Loss ◽

Biliopancreatic Diversion ◽

Fat Mass ◽

Fasting Blood Glucose ◽

Fasting Insulin ◽

Post Surgery ◽

Biliopancreatic Diversion Surgery

Introduction: Omentin-1 might play a role in the pathogenesis of insulin resistance and obesity. The aim of the present study was to evaluate the influence of weight loss after biliopancreatic diversion on serum omentin-1 concentrations. Material and Methods A Caucasian population of 24 morbid obese patients was analyzed before and after 12 months of a biliopancreatic diversion surgery. Biochemical and anthropometric evaluation were realized at basal visit and at 12 months. Body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1 were measured. Results: After bariatric surgery and in both gender groups (males vs. females); BMI, weight, fat mass, waist circumference, blood pressure, glucose , total cholesterol, LDL cholesterol, triglycerides, HOMA-IR and fasting insulin decreased in a statistical manner from basal values. Omentin-1 levels increased after bariatric surgery and in both gender the improvement was similar (males vs. females); (delta: –87.1 ± 19.0 ng/dL; p = 0.02 vs. –93.8 ± 28.1 ng/dL; p = 0.03). In the multiple regression analysis adjusted by age and sex; BMI kg/m2 (Beta –0.32: 95% CI –3.98 to –0.12) and insulin UI/L (Beta –0.41: 95% CI –8.38 to –0.16) remained in the model with basal omentin-1 levels as dependent variable. The regression model with post-surgery omentin-1 levels as dependent variable showed as independent variables BMI kg/m2 (Beta –0.13: 95% CI –7.69 to –0.09) and insulin UI/L (Beta –0.24: 95% CI –5.69 to –0.08), too. Conclusion: This study showed a significant increase in omentin-1 levels after weight loss secondary biliopancreatic diversion surgery. A weak negative correlation with BMI and basal insulin levels was detected.

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Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001686 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001686

Author(s):

Kaori Kitaoka ◽

Ayaka Tsuboi ◽

Satomi Minato-Inokawa ◽

Mari Honda ◽

Mika Takeuchi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Young Women ◽

Fat Mass ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Japanese Women ◽

Apolipoprotein A1 ◽

Middle Aged ◽

Diabetes And Obesity

IntroductionDeterminants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity.Research design and methodsCross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR.ResultsYoung and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women.ConclusionsAT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

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Loss of endothelin type B receptor function improves insulin sensitivity in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0666 ◽

2020 ◽

Vol 98 (9) ◽

pp. 604-610 ◽

Cited By ~ 2

Author(s):

Osvaldo J. Rivera-Gonzalez ◽

Malgorzata Kasztan ◽

Jermaine G. Johnston ◽

Kelly A. Hyndman ◽

Joshua S. Speed

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Body Mass ◽

Fat Mass ◽

Receptor Activation ◽

Separate Experiment ◽

Type B ◽

Epididymal Fat ◽

Significant Difference ◽

Etb Receptor

High salt intake (HS) is associated with obesity and insulin resistance. ET-1, a peptide released in response to HS, inhibits the actions of insulin on cultured adipocytes through ET-1 type B (ETB) receptors; however, the in vivo implications of ETB receptor activation on lipid metabolism and insulin resistance is unknown. We hypothesized that activation of ETB receptors in response to HS intake promotes dyslipidemia and insulin resistance. In normal salt (NS) fed rats, no significant difference in body mass or epididymal fat mass was observed between control and ETB deficient rats. After 2 weeks of HS, ETB-deficient rats had significantly lower body mass and epididymal fat mass compared to controls. Nonfasting plasma glucose was not different between genotypes; however, plasma insulin concentration was significantly lower in ETB-deficient rats compared to controls, suggesting improved insulin sensitivity. In addition, ETB-deficient rats had higher circulating free fatty acids in both NS and HS groups, with no difference in plasma triglycerides between genotypes. In a separate experiment, ETB-deficient rats had significantly lower fasting blood glucose and improved glucose and insulin tolerance compared to controls. These data suggest that ET-1 promotes adipose deposition and insulin resistance via the ETB receptor.

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