scholarly journals Relative adipose tissue failure in Alström syndrome drives obesity-induced insulin resistance

2020 ◽  
Author(s):  
Ada Admin ◽  
Tarekegn Geberhiwot ◽  
Shanat Baig ◽  
Cathy Obringer ◽  
Dorothée Girard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Therapeutic Strategies ◽  
Mice Model ◽  
Alström Syndrome ◽  
Monogenic Form ◽  
Depth Analysis ◽  
Alstrom Syndrome ◽  
Polygenic Obesity ◽  
First Time

Obesity is a major risk factor for insulin resistance (IR) and its attendant complications. The pathogenic mechanisms linking them remain poorly understood, partly due to a lack of intermediary monogenic human phenotypes. Here, we report on a monogenic form of IR-prone obesity, Alström syndrome (ALMS). Twenty-three subjects with monogenic or polygenic obesity underwent hyperinsulinaemic-euglycemic clamping with concomitant adipose tissue (AT) microdialysis and an in-depth analysis of subcutaneous AT histology. We have shown a relative adipose tissue failure in monogenic obese cohort; a finding supported by observations in a novel conditional mouse model (<i>Alms<sup>flin/flin</sup></i>) and ALMS1-silenced human primary adipocytes. Whereas, selective reactivation of ALMS1 gene in adipose tissue of an ALMS conditional knockdown mice model (<i>Alms<sup>flin/flin</sup>;Adipo-Cre<sup>+/-</sup></i>) restores systemic insulin sensitivity and glucose tolerance. Hence, we show for the first time the relative adipose tissue failure in human obese cohorts to be a major determinant of accelerated IR without evidence of lipodystrophy. These new insights into adipocyte driven insulin resistance may assist development of adipose tissue targeted therapeutic strategies for diabetes.

scholarly journals Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance

Diabetes ◽  
2020 ◽  
pp. db200647
Author(s):  
Tarekegn Geberhiwot ◽  
Shanat Baig ◽  
Cathy Obringer ◽  
Dorothée Girard ◽  
Charlotte Dawson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Alström Syndrome ◽  
Alstrom Syndrome

scholarly journals The Adipokines in Cancer Cachexia

2020 ◽  
Vol 21 (14) ◽  
pp. 4860 ◽  
Author(s):  
Michele Mannelli ◽  
Tania Gamberi ◽  
Francesca Magherini ◽  
Tania Fiaschi
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Therapeutic Strategies ◽  
Skeletal Muscle Wasting ◽  
Circulating Levels

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study in-depth the involvement of these hormones in this pathology could lead to the development of new therapeutic strategies.

scholarly journals Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome

2016 ◽  
Vol 36 (11) ◽  
pp. 1704-1712 ◽  
Author(s):  
Laura L. Gathercole ◽  
Jonathan M. Hazlehurst ◽  
Matthew J. Armstrong ◽  
Rachel Crowley ◽  
Sarah Boocock ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Tissue Fibrosis ◽  
Alström Syndrome ◽  
Alstrom Syndrome ◽  
Alcoholic Fatty Liver Disease

scholarly journals PATHOGENETIC ASPECTS OF THE PHENOTYPE OF BRONCHIAL ASTHMA ASSOCIATED WITH OBESITY

2019 ◽  
Vol 1 (71) ◽  
pp. 112-119
Author(s):  
А. Уксуменко ◽  
A. Uksumenko ◽  
Марина Антонюк ◽  
Marina Antonyuk
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Adipose Tissue ◽  
Gastroesophageal Reflux Disease ◽  
Respiratory Mechanics ◽  
Therapeutic Strategies ◽  
Obese Patients ◽  
Genetic Condition ◽  
Vitamin D Metabolism ◽  
Asthma Phenotype

Currently, in parallel with the increase in the prevalence of asthma, there is an increase in the number of obese patients. The results of numerous studies indicate that the asthma phenotype in combination with obesity has well-defined clinical features – a more severe course with frequent exacerbations and reduced control of the disease. The article considers the main pathogenetic mechanisms that determine the development of the asthma phenotype in combination with obesity. The influence of excess adipose tissue in the chest on respiratory mechanics, the correlation of gastroesophageal reflux disease and respiratory depression in sleep are described. It is shown that the phenotype of asthma with obesity is characterized by inflammation of adipose tissue, adipokine imbalance, insulin resistance, and disturbance of vitamin D metabolism. Gender peculiarities and genetic condition of asthma associated with obesity are considered. Understanding general mechanisms underlying the formation of asthma and obesity will undoubtedly contribute to the development of new therapeutic strategies.

scholarly journals Adipocyte Specific HO-1 Gene Therapy Is Effective in Antioxidant Treatment of Insulin Resistance and Vascular Function in an Obese Mice Model

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 40 ◽  
Author(s):  
Shailendra P. Singh ◽  
Menachem Greenberg ◽  
Yosef Glick ◽  
Lars Bellner ◽  
Gaia Favero ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gene Therapy ◽  
Adipose Tissue ◽  
Vascular Function ◽  
Therapeutic Approach ◽  
Vascular Dysfunction ◽  
Cellular Respiration ◽  
Heme Oxygenase 1 ◽  
Obese Mice ◽  
Mice Model

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity.

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