Comparison of independent and combined metabolic effects of chronic treatment with (pGlu-Gln)-CCK-8 and long-acting GLP-1 and GIP mimetics in high fat-fed mice

Sweeteners have become integrating components of the typical western diet, in response to the spreading of sugar-related pathologies (diabetes, obesity and metabolic syndrome) that have stemmed from the adoption of unbalanced dietary habits. Sweet proteins are a relatively unstudied class of sweet compounds that could serve as innovative sweeteners, but their introduction on the food market has been delayed by some factors, among which is the lack of thorough metabolic and toxicological studies. We have tried to shed light on the potential of a sweet protein, MNEI, as a fructose substitute in beverages in a typical western diet, by studying the metabolic consequences of its consumption on a Wistar rat model of high fat diet-induced obesity. In particular, we investigated the lipid profile, insulin sensitivity and other indicators of metabolic syndrome. We also evaluated systemic inflammation and potential colon damage. MNEI consumption rescued the metabolic derangement elicited by the intake of fructose, namely insulin resistance, altered plasma lipid profile, colon inflammation and translocation of lipopolysaccharides from the gut lumen into the circulatory system. We concluded that MNEI could represent a valid alternative to fructose, particularly when concomitant metabolic disorders such as diabetes and/or glucose intolerance are present.

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Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Diabetologia ◽

10.1007/s00125-013-2878-0 ◽

2013 ◽

Vol 56 (6) ◽

pp. 1425-1435 ◽

Cited By ~ 9

Author(s):

N. Irwin ◽

I. A. Montgomery ◽

P. R. Flatt

Keyword(s):

Receptor Activation ◽

Metabolic Effects ◽

High Fat ◽

Cck1 Receptor

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Metabolic effects of benzylidene thiazolidinedione derivatives in high-fat fed mice

Medicinal Chemistry Research ◽

10.1007/s00044-011-9764-4 ◽

2011 ◽

Vol 21 (9) ◽

pp. 2408-2414 ◽

Cited By ~ 4

Author(s):

Tiago Gomes Araújo ◽

Bruno Melo Carvalho ◽

Caíque Silveira Martins da Fonseca ◽

Maria do Carmo Alves de Lima ◽

Suely Lins Galdino ◽

...

Keyword(s):

Metabolic Effects ◽

High Fat

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Abstract 037: Role of Pro-opiomelanocortin (POMC) Specific PTP1B in Differential Regulation of Blood Pressure, Liver Lipid Accumulation and Glucose Tolerance in Response to a High Fat Diet

Hypertension ◽

10.1161/hyp.68.suppl_1.037 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Nicola Aberdein ◽

Jussara M do Carmo ◽

Zhen Wang ◽

Taolin Fang ◽

Cecilia P de Lara ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Fat Mass ◽

Lipid Accumulation ◽

High Fat Diet ◽

Acute Stress ◽

Liver Lipid ◽

Liver Weight ◽

Metabolic Effects ◽

High Fat

Obese subjects are often resistant to leptin’s metabolic effects although blood pressure (BP) and sympathetic nervous system responses appear to be preserved. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin signaling, may play a role in promoting this selective leptin resistance and causing metabolic dysfunction in obesity. Our previous studies suggest that the chronic BP responses to leptin are mediated via activation of pro-opiomelanocortin (POMC) neurons. The goal of this study was to determine if PTP1B in POMC neurons differentially controls metabolic functions and BP in mice fed a high fat diet (HFD). Male mice with POMC specific PTP1B deletion (POMC/PTP1B -/- ) and littermate controls (PTP1B flox/flox ) were fed a HFD from 6 to 22 wks of age. Baseline BP after 16 weeks of a HFD (95±2 vs. 95±3 mmHg) and BP responses to acute stress (Δ32±0 vs. Δ32±6 mmHg), measured by telemetry, were not different in POMC/PTP1B -/- compared to control mice, respectively. Heart rate (HR) was not different in POMC/PTP1B -/- and control mice during acute stress (699±4 vs. 697±15 bpm, respectively). Total body weight (TBW) and fat mass were reduced at 20 weeks of age in POMC/PTP1B -/- compared to controls (36.7±0.1 vs. 42.0±1 g TBW and 12.7±0.4 vs. 16.1±1.0 g fat mass, respectively). Liver weight of POMC/PTP1B -/- mice was less than in controls, and this was evident even when liver weight was normalized as % of TBW (4.5±0.2 vs. 5.0±0.2 %). POMC/PTP1B -/- males had reduced liver lipid accumulation compared to controls as measured by EchoMRI (0.08±0.03 vs. 0.15±0.03 g/g liver weight). Glucose tolerance was also improved by 46% in POMC/PTP1B -/- compared to controls as measured by AUC, 25856±1683 vs. 47267±5616 mg/dLx120min, respectively. These findings indicate that PTP1B signaling in POMC neurons plays a crucial role in regulating liver lipid accumulation and glucose tolerance but does not appear to mediate changes in BP or BP responses to acute stress in mice fed a high HFD (supported by NHLBI-PO1HL51971 and NIGMS P20GM104357)

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Probiotics lower plasma glucose in the high-fat fed C57BL/6J mouse

Beneficial Microbes ◽

10.3920/bm2009.0036 ◽

2010 ◽

Vol 1 (2) ◽

pp. 189-196 ◽

Cited By ~ 59

Author(s):

U. Andersson ◽

C. Bränning ◽

S. Ahrné ◽

G. Molin ◽

J. Alenfall ◽

...

Keyword(s):

Gut Microbiota ◽

Plasma Glucose ◽

Short Chain Fatty Acids ◽

Tolerance Test ◽

Metabolic Effects ◽

Control Group ◽

Oral Glucose ◽

Gut Health ◽

High Fat ◽

Early Diabetes

Today, the gut microbiota is considered a key organ in host nutritional metabolism and recent data have suggested that alterations in gut microbiota contribute to the development of type 2 diabetes and obesity. Accordingly, a whole range of beneficial effects relating to inflammation and gut health have been observed following administration of probiotics to both humans and different animal models. The objective of this study was to evaluate the metabolic effects of an oral probiotic supplement, Lactobacillus plantarum DSM 15313, to high-fat diet (HFD) fed C57BL/6J mice, a model of human obesity and early diabetes. The mice were fed the experimental diets for 20 weeks, after which the HFD had induced an insulin-resistant state in both groups compared to the start of the study. The increase in body weight during the HFD feeding was higher in the probiotic group than in the control group, however, there were no significant differences in body fat content. Fasting plasma glucose levels were lower in the group fed the probiotic supplement, whereas insulin and lipids were not different. Caecal levels of short-chain fatty acids were not significantly different between the groups. An oral glucose tolerance test showed that the group fed probiotics had a significantly lower insulin release compared to the control group, although the rate of glucose clearance was not different. Taken together, these data indicate that L. plantarum DSM 15313 has anti-diabetic properties when fed together with an HFD.

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Poliphenolic-rich extracts from cocoa (Theobroma cacao L.) and cupuassu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) liquors: A comparison of metabolic effects in high-fat fed rats

PharmaNutrition ◽

10.1016/j.phanu.2015.01.002 ◽

2015 ◽

Vol 3 (2) ◽

pp. 20-28 ◽

Cited By ~ 9

Author(s):

Thiago Belchior de Oliveira ◽

Marcelo Macedo Rogero ◽

Maria Inés Genovese

Keyword(s):

Theobroma Cacao ◽

Metabolic Effects ◽

High Fat ◽

Theobroma Grandiflorum ◽

Theobroma Cacao L

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Sexual dimorphism in hypothalamic inflammation in the offspring of dams exposed to a diet rich in high fat and branched-chain amino acids

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00183.2019 ◽

2019 ◽

Vol 317 (3) ◽

pp. E526-E534 ◽

Cited By ~ 1

Author(s):

Marianna Sadagurski ◽

Lucas Kniess Debarba ◽

Joao Pedro Werneck-de-Castro ◽

Abear Ali Awada ◽

Tess A. Baker ◽

...

Keyword(s):

Energy Homeostasis ◽

Maternal Nutrition ◽

Inflammatory Responses ◽

Maternal Diet ◽

Female Offspring ◽

Metabolic Effects ◽

Standard Diet ◽

High Fat ◽

Hypothalamic Inflammation ◽

Branched Chain

Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.

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Adiponectin is required to mediate rimonabant-induced improvement of insulin sensitivity but not body weight loss in diet-induced obese mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90824.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R929-R935 ◽

Cited By ~ 29

Author(s):

Stéphanie Migrenne ◽

Amélie Lacombe ◽

Anne-Laure Lefèvre ◽

Marie-Pierre Pruniaux ◽

Etienne Guillot ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Energy Homeostasis ◽

Hepatic Glucose Production ◽

Body Weight Loss ◽

Metabolic Effects ◽

Wild Type ◽

High Fat ◽

Wild Type Littermate

The increase in adiponectin levels in obese patients with untreated dyslipidemia and its mRNA expression in adipose tissue of obese animals are one of the most interesting consequences of rimonabant treatment. Thus, part of rimonabant's metabolic effects could be related to an enhancement of adiponectin secretion and its consequence on the modulation of insulin action, as well as energy homeostasis. The present study investigated the effects of rimonabant in adiponectin knockout mice (Ad−/−) exposed to diet-induced obesity conditions. Six-week-old Ad−/− male mice and their wild-type littermate controls (Ad+/+) were fed a high-fat diet for 7 mo. During the last month, animals were administered daily either with vehicle or rimonabant by mouth (10 mg/kg). High-fat feeding induced weight gain by about 130% in both wild-type and Ad−/− mice. Obesity was associated with hyperinsulinemia and insulin resistance. Treatment with rimonabant led to a significant and similar decrease in body weight in both Ad+/+ and Ad−/− mice compared with vehicle-treated animals. In addition, rimonabant significantly improved insulin sensitivity in Ad+/+ mice compared with Ad+/+ vehicle-treated mice by decreasing hepatic glucose production and increasing glucose utilization index in both visceral and subcutaneous adipose tissue. In contrast, rimonabant failed to improve insulin sensitivity in Ad−/− mice, despite the loss in body weight. Rimonabant's effect on body weight appeared independent of the adiponectin pathway, whereas adiponectin seems required to mediate rimonabant-induced improvement of insulin sensitivity in rodents.

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