scholarly journals β-arrestin-1 suppresses myogenic reprogramming of brown fat to maintain euglycemia

2020 ◽  
Vol 6 (23) ◽  
pp. eaba1733 ◽  
Author(s):  
Sai P. Pydi ◽  
Shanu Jain ◽  
Luiz F. Barella ◽  
Lu Zhu ◽  
Wataru Sakamoto ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Peripheral Tissues ◽  
Nuclear Signaling ◽  
Brown Adipose ◽  
Calorie Diet ◽  
Obesogenic Diet ◽  
Obesity Drugs ◽  
High Calorie

A better understanding of the signaling pathways regulating adipocyte function is required for the development of new classes of antidiabetic/obesity drugs. We here report that mice lacking β-arrestin-1 (barr1), a cytoplasmic and nuclear signaling protein, selectively in adipocytes showed greatly impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet. In contrast, transgenic mice overexpressing barr1 in adipocytes were protected against the metabolic deficits caused by a high-calorie diet. Barr1 deficiency led to a myogenic reprogramming of brown adipose tissue (BAT), causing elevated plasma myostatin (Mstn) levels, which in turn led to impaired insulin signaling in multiple peripheral tissues. Additional in vivo studies indicated that barr1-mediated suppression of Mstn expression by BAT is required for maintaining euglycemia. These findings convincingly identify barr1 as a critical regulator of BAT function. Strategies aimed at enhancing barr1 activity in BAT may prove beneficial for the treatment of type 2 diabetes.

Cold acclimation-recruited nonshivering thermogenesis: the Syrian hamster is not an exception

1995 ◽  
Vol 269 (4) ◽  
pp. R767-R774 ◽  
Author(s):  
A. Dicker ◽  
B. Cannon ◽  
J. Nedergaard
Keyword(s):  
Metabolic Rate ◽  
Cold Acclimation ◽  
Resting Metabolic Rate ◽  
High Rate ◽  
In Vivo Studies ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose ◽  
Thermogenic Response

Biochemical evidence from in vitro studies of brown adipose tissue in Syrian hamsters indicates a significant degree of recruitment of the tissue as an effect of cold acclimation. However, earlier in vivo studies indicate a lack of recruitment of nonshivering thermogenesis in the intact animal as a result of cold acclimation. Because of this apparent discrepancy, the occurrence of cold acclimation-recruited nonshivering thermogenesis in hamsters was investigated. Hamsters were cold acclimated to 6 degrees C or remained at 24 degrees C (controls), and their thermogenic response was investigated in an open-circuit system at 24 degrees C. Cold acclimation resulted in a small increase in resting metabolic rate and a major increase in the thermogenic response to norepinephrine (61% increase over resting metabolic rate in controls and 156% increase in cold-acclimated animals). The absolute beta 3-specific adrenergic agonist CGP-12177 also induced a high rate of nonshivering thermogenesis, which was similarly recruited. It was concluded that, concerning the relative effect of recruitment on the capacity for nonshivering thermogenesis, the intact hamsters responded as would be predicted from in vitro experiments. Thus the hamster does not seem to constitute an exception to the general patterns described for other rodents concerning recruitment of nonshivering thermogenesis due to cold acclimation.

scholarly journals Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 188 ◽  
Author(s):  
Filip Vlavcheski ◽  
Mariah Young ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Pathological Condition ◽  
Current Treatment ◽  
In Vivo Studies ◽  
Olive Leaves ◽  
Treatment And Prevention ◽  
Antidiabetic Effects

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

Molecular determinants of PPARγ partial agonism and related in silico/in vivo studies of natural saponins as potential type 2 diabetes modulators

2018 ◽  
Vol 112 ◽  
pp. 47-59 ◽  
Author(s):  
Merilin Al Sharif ◽  
Petko Alov ◽  
Antonia Diukendjieva ◽  
Vessela Vitcheva ◽  
Rumyana Simeonova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
In Silico ◽  
In Vivo Studies ◽  
Partial Agonism ◽  
Potential Type ◽  
Molecular Determinants

Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

2019 ◽  
Vol 51 (10) ◽  
pp. 671-677 ◽  
Author(s):  
Maurício Martins da Silva ◽  
Carlos Frederico Lima Gonçalves ◽  
Leandro Miranda-Alves ◽  
Rodrigo Soares Fortunato ◽  
Denise P. Carvalho ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormone ◽  
Bisphenol A ◽  
Brown Adipose Tissue ◽  
Tissue Type ◽  
Deiodinase Activity ◽  
Brown Adipose

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

scholarly journals Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors

2021 ◽  
Vol 23 (1) ◽  
pp. 322
Author(s):  
Maria N. Evseeva ◽  
Maria S. Balashova ◽  
Konstantin Y. Kulebyakin ◽  
Yury P. Rubtsov
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Metabolic Disorders ◽  
Adipogenic Differentiation ◽  
In Vivo Studies ◽  
Research Review ◽  
Treatment And Prevention

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

scholarly journals Dynamic of Glucose Homeostasis in Virtual Patients: A Comparison between Different Behaviors

2022 ◽  
Vol 19 (2) ◽  
pp. 716
Author(s):  
Alexis Alonso-Bastida ◽  
Manuel Adam-Medina ◽  
Rubén Posada-Gómez ◽  
Dolores Azucena Salazar-Piña ◽  
Gloria-Lilia Osorio-Gordillo ◽  
...  
Keyword(s):  
Physical Activity ◽  
Glucose Homeostasis ◽  
Sedentary Lifestyle ◽  
In Vivo Studies ◽  
Virtual Patients ◽  
Healthy Individuals ◽  
In Vivo Experiments ◽  
Glucose Dynamics

This work presents a mathematical model of homeostasis dynamics in healthy individuals, focusing on the generation of conductive data on glucose homeostasis throughout the day under dietary and physical activity factors. Two case studies on glucose dynamics for populations under conditions of physical activity and sedentary lifestyle were developed. For this purpose, two types of virtual populations were generated, the first population was developed according to the data of a total of 89 physical persons between 20 and 75 years old and the second was developed using the Monte Carlo approach, obtaining a total of 200 virtual patients. In both populations, each participant was classified as an active or sedentary person depending on the physical activity performed. The results obtained demonstrate the capacity of virtual populations in the generation of in-silico approximations similar to those obtained from in-vivo studies. Obtaining information that is only achievable through specific in-vivo experiments. Being a tool that generates information for the approach of alternatives in the prevention of the development of type 2 Diabetes.

scholarly journals Potential Usefulness of a Wakame/Carob Functional Snack for the Treatment of Several Aspects of Metabolic Syndrome: From In Vitro to In Vivo Studies

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 512 ◽  
Author(s):  
Cristina Martínez-Villaluenga ◽  
Elena Peñas ◽  
Daniel Rico ◽  
Ana Martin-Diana ◽  
Maria Portillo ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Potential Usefulness ◽  
In Vivo Studies ◽  
Raw 264.7 Macrophages ◽  
Anti Inflammatory ◽  
Carob Pod ◽  
First Time

Metabolic syndrome (MetS) greatly increases the risk of cardiovascular diseases and type 2 diabetes mellitus. The aim of this study was to evaluate the efficacy of functional snacks containing a combination of wakame (W) and carob pod (CP) flours in reducing markers associated with MetS. The mechanisms of action underlying these effects were also evaluated. In vitro approaches were carried out in mature 3T3-L1 adipocytes and RAW 264.7 macrophages treated with different doses of extracts from W, CP, or a combination of both. Furthermore, an in vivo experiment was conducted in rats with MetS treated with normal-caloric diets containing different snack formulations with combinations of 1/50 (snack A) or 1/5 of wakame/carob (snack B). In vitro experiments results indicated that both W and CP had delipidating effects, but only the latter induced anti-inflammatory and anti-hypertensive effects. As far as the in vivo study is concerned, snack B was ineffective and snack A showed an anti-hypertensive effect in rats with MetS. The present study shows for the first time the in vitro efficacy of a W and CP combination as an anti-inflammatory, delipidating, and anti-hypertensive tool, and its potential usefulness in treating MetS.

scholarly journals Nanotechnology advances towards development of targeted-treatment for obesity

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicole Remaliah Samantha Sibuyi ◽  
Koena Leah Moabelo ◽  
Mervin Meyer ◽  
Martin Opiyo Onani ◽  
Admire Dube ◽  
...  
Keyword(s):  
Lifestyle Modification ◽  
Mortality Rates ◽  
Proof Of Concept ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Inhibition Of Angiogenesis ◽  
Healthy Body Weight ◽  
Treatment Of Obesity ◽  
Obesity Drugs

AbstractObesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modification or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specificity and unsustainable weight loss effects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side effects, and enhanced efficacy. These effects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbidities.

scholarly journals Antidiabetic Properties of Curcumin II: Evidence from In Vivo Studies

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 58 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Alessandra Gabriel ◽  
Evangelia Tsiani
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Insulin Resistance ◽  
Fruits And Vegetables ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
Current Review ◽  
Antidiabetic Effects

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment approaches to insulin resistance and T2DM lack in efficacy, resulting in the need for new approaches to prevent and treat the disease. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects, including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (II of II) summarizes the existing in vivo studies examining the antidiabetic effects of curcumin.

scholarly journals Increased Postprandial GIP and Glucagon Responses, But Unaltered GLP-1 Response after Intervention with Steroid Hormone, Relative Physical Inactivity, And High-Calorie Diet in Healthy Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. 447-453 ◽  
Author(s):  
Katrine B. Hansen ◽  
Tina Vilsbøll ◽  
Jonatan I. Bagger ◽  
Jens J. Holst ◽  
Filip K. Knop
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Physical Inactivity ◽  
Postprandial Glucose ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

abstract Objective: Increased postprandial glucose-dependent insulinotropic polypeptide (GIP) and glucagon responses and reduced postprandial glucagon-like peptide-1 (GLP-1) responses have been observed in some patients with type 2 diabetes mellitus. The causality of these pathophysiological traits is unknown. We aimed to determine the impact of insulin resistance and reduced glucose tolerance on postprandial GIP, GLP-1, and glucagon responses in healthy subjects. Research Design and Methods: A 4-h 2200 KJ-liquid meal test was performed in 10 healthy Caucasian males without family history of diabetes [age, 24 ± 3 yr (mean ± sd); body mass index, 24 ± 2 kg/m2; fasting plasma glucose, 4.9 ± 0.3 mm; hemoglobin A1c, 5.4 ± 0.1%] before and after intervention using high-calorie diet, relative physical inactivity, and administration of prednisolone (37.5 mg/d) for 12 d. Results: The intervention resulted in insulin resistance according to the homeostatic model assessment [1.1 ± 0.3 vs. 2.3 (mean ± sem) ± 1.3; P = 0.02] and increased postprandial glucose excursions [area under curve (AUC), 51 ± 28 vs. 161 ± 32 mm · 4 h; P = 0.045], fasting plasma insulin (36 ± 3 vs. 61 ± 6 pm; P = 0.02), and postprandial insulin responses (AUC, 22 ± 6 vs. 43 ± 13 nm · 4 h; P = 0.03). This disruption of glucose homeostasis had no impact on postprandial GLP-1 responses (AUC, 1.5 ± 0.7 vs. 2.0 ± 0.5 nm · 4 h; P = 0.56), but resulted in exaggerated postprandial GIP (6.2 ± 1.0 vs. 10.0 ± 1.3 nm · 4 h; P = 0.003) and glucagon responses (1.6 ± 1.5 vs. 2.4 ± 3.2; P = 0.007). Conclusions: These data suggest that increased postprandial GIP and glucagon responses may occur as a consequence of insulin resistance and/or reduced glucose tolerance. Our data suggest that acute disruption of glucose homeostasis does not result in reduced postprandial GLP-1 responses as observed in some individuals with type 2 diabetes mellitus.

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