Azoxymethane-Induced Colorectal Cancer Mice Treated with a Polyphenol-Rich Apple Extract Show Less Neoplastic Lesions and Signs of Cachexia

Obesity is considered a risk factor for the development of colorectal cancer. In rodents, high-fat (HF) diets are able to increase the formation of azoxymethane (AOM)-induced polyps. Polyphenol-rich apple extracts have antioxidant and anti-inflammatory activities and may induce an amelioration of the manifestations of colorectal cancer. Twenty-seven male Crl:CD-1 mice received AOM during four weeks and were subsequently divided into three groups fed a HF diet (n = 9 each group): a non-supplemented group, a second group supplemented with apple extract at 1%, and a third group supplemented with the same apple extract at 1.5%. Energy metabolism and the respiratory quotient were not affected by the supplementation with the apple extract. Although body weight was not affected by the treatment, the mice supplemented with the apple extract showed less signs of cachexia than the non-treated mice. In the intestine, the mice supplemented with the apple extract showed lower sucrase, dipeptidyl-peptidase IV, and aminopeptidase N activities, and less intestinal lesions (aberrant crypt foci and polyps). Administration of a polyphenol-rich apple extract reduces the number of neoplastic lesions in mice with AOM-induced colorectal cancer and contributes to preserve adipose tissue mass.

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Prophylactic and therapeutic effects of different doses of vitamin C on high-fat-diet-induced non-alcoholic fatty liver disease in mice

10.21203/rs.3.rs-20940/v1 ◽

2020 ◽

Author(s):

Qingmin Zeng ◽

Lili Zhao ◽

Chao Meng ◽

Xiaotong Zhao ◽

Yonggang Liu ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Therapeutic Effects ◽

High Fat ◽

Tissue Mass ◽

Alcoholic Fatty Liver ◽

Perirenal Adipose Tissue ◽

Adipose Tissue Mass ◽

Lobular Inflammation ◽

Different Doses

Abstract Background: Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). However, the intervention dose of Vc and the mechanisms of its action in NAFLD are unclear. This study aimed to investigate the prophylactic and therapeutic effects of low, medium and high doses of Vc on NAFLD. Methods: C57BL/6 mice were randomly assigned to prophylactic groups or therapeutic groups. Each group had five subgroups: control subgroup (C), high-fat subgroup (HF), low-dose Vc subgroup (15 mg/kg per day, LVc), medium-dose Vc subgroup (30 mg/kg per day, MVc), and high-dose Vc subgroup (90 mg/kg per day, HVc). In prophylactic groups, mice received high-fat diet (HFD) and simultaneously supplied with different doses Vc for 12 weeks. In therapeutic groups, mice were fed HFD for 6 weeks to form NAFLD model, and then treated with different dose Vc for 12 weeks. Results: Prophylactic LVc and MVc administration reduced the risk of NAFLD development in HFD-fed mice, as evidenced by significantly lowered body weight, perirenal adipose tissue mass, and steatosis, whereas prophylactic HVc administration did not prevent HFD-induced NAFLD development. Furthermore, therapeutic MVc administration significantly ameliorated HFD-induced increase in body weight, perirenal adipose tissue mass and steatosis, whereas therapeutic LVc and HVc administration did not ameliorate NAFLD symptoms. In fact, therapeutic HVc administration significantly increased body weight, perirenal adipose tissue mass and lobular inflammation. Moreover, prophylactic LVc administration was more effective than therapeutic LVc administration as evidenced by significantly lower body weight, perirenal adipose tissue mass, steatosis, ballooned hepatocytes, and lobular inflammation in the prophylactic LVc subgroup. And same trends were observed between prophylactic HVc administration and therapeutic HVc administration. In addition, all Vc-administered mice exhibited low blood glucose, triglycerides, and homeostasis model assessment of insulin resistance values and high adiponectin levels compared to HF mice. Conclusion: MVc was beneficial for HFD-induced NAFLD prophylaxis and therapy. LVc prevented HFD-induced NAFLD development, while HVc for NAFLD management was risky. This study offers valuable insight into the effect of various Vc doses on NAFLD management.

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Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00628-5 ◽

2021 ◽

Author(s):

Won-Il Choi ◽

Jae-Hyun Yoon ◽

Seo-Hyun Choi ◽

Bu-Nam Jeon ◽

Hail Kim ◽

...

Keyword(s):

Lipid Metabolism ◽

High Fat Diet ◽

Target Genes ◽

Proximal Promoter ◽

High Fat ◽

Tissue Mass ◽

Adipose Tissues ◽

Adipose Tissue Mass ◽

Age Dependent ◽

Treatment Of Diabetes

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

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Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2014.06.003 ◽

2014 ◽

Vol 393 (1-2) ◽

pp. 120-128 ◽

Cited By ~ 6

Author(s):

M. Holubová ◽

V. Nagelová ◽

Z. Lacinová ◽

M. Haluzík ◽

D. Sýkora ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Food Intake ◽

Tissue Mass ◽

Adipose Tissue Mass

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Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity

10.1101/834416 ◽

2019 ◽

Author(s):

Lidewij Schipper ◽

Steffen van Heijningen ◽

Giorgio Karapetsas ◽

Eline M. van der Beek ◽

Gertjan van Dijk

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Intake ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Tissue Mass ◽

Individual Housing ◽

Adipose Tissue Mass ◽

Obesogenic Diet

AbstractIndividual housing from weaning onwards resulted in reduced growth rate during adolescence in male C57Bl/6J mice that were housed individually, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice. Body weight gain of individually housed animals exceeded that of socially housed mice during adulthood, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition. This study shows that post-weaning individual housing of male mice results in impaired adolescent growth and higher susceptibility to obesity in adulthood. Mice are widely used to study obesity and cardiometabolic comorbidities. For (metabolic) research models using mice, (social) housing practices should be carefully considered and regarded as a potential confounder due to their modulating effect on metabolic health outcomes.

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High-fat and low-fat (behavioural) phenotypes: biology or environment?

Proceedings of The Nutrition Society ◽

10.1017/s0029665199001056 ◽

1999 ◽

Vol 58 (4) ◽

pp. 773-777 ◽

Cited By ~ 26

Author(s):

John E. Blundell ◽

John Cooling

Keyword(s):

Risk Factors ◽

Body Weight ◽

Risk Factor ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

Positive Energy ◽

High Fat ◽

Low Fat ◽

Conceptual Tool

It is now widely accepted that obesity develops by way of genetic mechanisms conferring specific dispositions which interact with strong environmental pressures. It is also accepted that certain dispositions constitute metabolic risk factors for weight gain. It is less well accepted that certain patterns of behaviour (arising from biological demands or environmental influences) put individuals at risk of developing a positive energy balance and weight gain (behavioural risk factors). Relevant patterns of behaviour include long-lasting habits for selecting and eating particular types of foods. Such habits define two distinct groups characterized as high-fat (HF) and low-fat (LF) phenotypes. These habits are important because of the attention given to dietary macronutrients in body-weight gain and the worldwide epidemic of obesity. Considerable evidence indicates that the total amount of dietary fat consumed remains the most potent food-related risk factor for weight gain. However, although habitual intake of a high-fat diet is a behavioural risk factor for obesity, it does not constitute a biological inevitability. A habitual low-fat diet does seem to protect against the development of obesity, but a high-fat diet does not guarantee that an individual will be obese. Although obesity is much more prevalent among HF than LF, some HF are lean with BMI well within the normal range. The concept of 'different routes to obesity' through a variety of nutritional scenarios can be envisaged, with predisposed individuals varying in their susceptibility to different dietary inputs. In a particular subgroup of individuals (young adult males) HF and LF displayed quite different profiles of appetite control, response to nutrient challenges and physiological measures, including BMR, RQ, heart rate, plasma leptin levels and thermogenic responses to fat and carbohydrate meals. These striking differences suggest that HF and LF can be used as a conceptual tool to investigate the relationship between biology and the environment (diet) in the control of body weight.

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Effect of VPAC1 Blockade on Adipose Tissue Formation and Composition in Mouse Models of Nutritionally Induced Obesity

Journal of Obesity ◽

10.1155/2010/359527 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

H. Roger Lijnen ◽

Kathleen Freson ◽

Marc F. Hoylaerts

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Mouse Models ◽

Tissue Formation ◽

Tissue Mass ◽

Diet Induced Obesity ◽

Pituitary Adenylate Cyclase ◽

Adipose Tissue Mass ◽

Adipocyte Hypertrophy ◽

G Protein Coupled

Background. The pituitary adenylate cyclase activating polypeptide (PACAP) may affect adipogenesis and adipose tissue formation through interaction with its G-protein-coupled receptor VPAC1.Methods. We have used a monoclonal antibody (MAb 23A11) blocking VPAC1 in mouse models of nutritionally induced obesity.Results. Administration of MAb 23A11 (25 mg/kg body weight i.p. twice weekly) to 5-week old male C57Bl/6 mice kept on a high-fat diet for 15 weeks had no significant effect on weight gain, nor on subcutaneous (SC) or gonadal (GON) adipose tissue mass, as compared to the control MAb 1C8. However, adipocyte hypertrophy was observed in SC adipose tissue of MAb 23A11 treated mice. In a second study, 24 weeks old obese mice were treated for 5 weeks with MAb 23A11, without effect on body weight or fat mass, as compared to treatment with MAb 1C8. In addition, MAb 23A11 had no significant effect on glucose tolerance or insulin resistance in lean or obese C57Bl/6 mice.Conclusion. Blocking VPAC1 does not significantly affect adipose tissue formation in mouse models of diet-induced obesity, although it may be associated with mild adipocyte hypertrophy.

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Activation of the adipocyte CREB/CRTC pathway in obesity

Communications Biology ◽

10.1038/s42003-021-02735-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Young-Sil Yoon ◽

Weiyi Liu ◽

Sam Van de Velde ◽

Shigenobu Matsumura ◽

Ezra Wiater ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

High Fat Diet ◽

Type Ii Diabetes ◽

High Fat ◽

Tissue Mass ◽

Pparγ Agonist ◽

Adipose Tissue Mass ◽

Factor C ◽

Pro Inflammatory Cytokines

AbstractObesity is a major risk factor for the development of type II diabetes. Increases in adipose tissue mass trigger insulin resistance via the release of pro-inflammatory cytokines from adipocytes and macrophages. CREB and the CRTC coactivators have been found to promote insulin resistance in obesity, although the mechanism is unclear. Here we show that high fat diet feeding activates the CREB/CRTC pathway in adipocytes by decreasing the expression of SIK2, a Ser/Thr kinase that phosphorylates and inhibits CRTCs. SIK2 levels are regulated by the adipogenic factor C/EBPα, whose expression is reduced in obesity. Exposure to PPARγ agonist rescues C/EBPα expression and restores SIK2 levels. CRTC2/3 promote insulin resistance via induction of the chemokines CXCL1/2. Knockout of CRTC2/3 in adipocytes reduces CXCL1/2 expression and improves insulin sensitivity. As administration of CXCL1/2 reverses salutary effects of CRTC2/3 depletion, our results demonstrate the importance of the CREB/CRTC pathway in modulating adipose tissue function.

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Chronic intermittent hypobaric hypoxia improves markers of iron metabolism in a model of dietary-induced obesity

Journal of Inflammation ◽

10.1186/s12950-020-00265-1 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Fang Cui ◽

Jing Guo ◽

Hao-Fei Hu ◽

Yi Zhang ◽

Min Shi

Keyword(s):

Body Weight ◽

Risk Factor ◽

Mrna Expression ◽

Iron Metabolism ◽

Hypobaric Hypoxia ◽

The Body ◽

High Fat ◽

Intermittent Hypobaric Hypoxia ◽

Obese Rats ◽

Hepcidin Mrna

Abstract Background Obesity, a risk factor for many chronic diseases, is a potential independent risk factor for iron deficiency. Evidence has shown that chronic intermittent hypobaric hypoxia (CIHH) has protective or improved effects on cardiovascular, nervous, metabolic and immune systems. We hypothesized that CIHH may ameliorate the abnormal iron metabolism in obesity. This study was aimed to investigate the effect and the underlying mechanisms of CIHH on iron metabolism in high-fat-high-fructose-induced obese rats. Methods Six to seven weeks old male Sprague-Dawley rats were fed with different diet for 16 weeks, and according to body weight divided into four groups: control (CON), CIHH (28-day, 6-h daily hypobaric hypoxia treatment simulating an altitude of 5000 m), dietary-induced obesity (DIO; induced by high fat diet and 10% fructose water feeding), and DIO + CIHH groups. The body weight, systolic arterial pressure (SAP), Lee index, fat coefficient, blood lipids, blood routine, iron metabolism parameters, interleukin6 (IL-6) and erythropoietin (Epo) were measured. The morphological changes of the liver, kidney and spleen were examined. Additionally, hepcidin mRNA expression in liver was analyzed. Results The DIO rats displayed obesity, increased SAP, lipids metabolism disorders, damaged morphology of liver, kidney and spleen, disturbed iron metabolism, increased IL-6 level and hepcidin mRNA expression, and decreased Epo compared to CON rats. But all the aforementioned abnormalities in DIO rats were improved in DIO + CIHH rats. Conclusions CIHH improves iron metabolism disorder in obese rats possibly through the down-regulation of hepcidin by decreasing IL-6 and increasing Epo.

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Activation of adipose tissue glycerokinase contributes to increased white adipose tissue mass in mice fed a high-fat diet

Endocrine ◽

10.1007/s12020-020-02288-3 ◽

2020 ◽

Vol 69 (1) ◽

pp. 79-91

Author(s):

Samyra Lopes Buzelle ◽

Franciele Przygodda ◽

Rafael Rossi-Valentim ◽

Graziella Nascimento Ferreira ◽

Maria Antonieta Rissato Garófalo ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Tissue Mass ◽

Adipose Tissue Mass

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Step-Defined Physical Activity Is Associated With Weight Loss and Changes in Body Composition and Fat Distribution in Response to Diet Interventions: The POUNDS Lost Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzab055_069 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1259-1259

Author(s):

Qiaochu Xue ◽

Xiang Li ◽

Hao Ma ◽

Tao Zhou ◽

Yoriko Heianza ◽

...

Keyword(s):

Physical Activity ◽

Weight Loss ◽

Body Composition ◽

Body Weight ◽

Body Fat ◽

Fat Distribution ◽

Tissue Mass ◽

Adipose Tissue Mass ◽

Fat Composition ◽

Protein Diets

Abstract Objectives To examine whether objectively measured physical activity (PA) is associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions. Methods This study included 535 overweight or obese participants randomly assigned to 4 weight-loss diets varying in macronutrient intake with physical activity measured objectively with pedometers in the POUNDS Lost trial. The associations of step defined PA or the changes in PA with the changes in obesity measurements including body weight (BW), waist circumference (WC), body fat composition assessed by the dual-energy X-ray absorptiometry (DEXA) scans, body fat distribution assessed by the computed tomography (CT) were examined at the 6 and 24 months. We also examined whether the associations were modified by diet interventions. Results The increase of step-defined PA was significantly predictive of weight loss and decrease in all measurements of body fat composition and distribution in response to diet interventions over 24 months (P < 0.0001 for all). We also observed significant inverse associations of changes in PA with changes in BW (P < 0.0001), WC (P < 0.0001), body fat composition (P < 0.05 for total fat, total lean, total fat mass %, and trunk fat %) and fat distribution (P < 0.05 for total adipose tissue mass (TAT), visceral adipose tissue mass (VAT), deep subcutaneous adipose tissue mass (DSAT)) from baseline to 6 months, when the maximum weight loss was achieved. Dietary fat or protein intake modified the associations between changes in PA and changes in body weight and waist circumference over 24 months; greater reduction in these measures was observed in participants with high-fat or low-protein diets than those in the low-fat or high-protein diets (P interaction < 0.05 for all). Conclusions Our results indicate that objectively measured PA is inversely related to the changes in body weight, body composition, and fat distribution in response to weight-loss diets, and such relation is more evident in people with high-fat or low-protein diets. Funding Sources The study was supported by grants from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Fogarty International Center, and Tulane Research Centers of Excellence Awards.

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