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- Dipta, P., et al.
(författare)
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Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes
- 2021
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Ingår i: Comprehensive Psychoneuroendocrinology. - : Elsevier BV. - 2666-4976. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Olanzapine and Aripiprazole are widely used second-generation antipsychotic drugs. Olanzapine, more than Aripiprazole, leads to considerable metabolic side effects including obesity and diabetes. While the underlying mechanisms are not fully understood, these side effects are likely associated with mild inflammation in the metabolic organs. An in vitro model that accurately recapitulates the metabolic impact of olanzapine and aripiprazole should be useful to elucidate the underlying mechanisms. Methods: We established co-cultures of matured adipocytes derived from the human SGBS cell line and the THP-1 human monocytic cell-derived or primary macrophages to explore the effects of both drugs on the response to insulin. Results: Olanzapine, but not aripiprazole induced insulin resistance in SGBS adipocytes only when co-cultured with THP-1 or primary macrophages, polarized either into M0, M1 or M2. Noteworthy, M2 macrophages induced olanzapine-dependent insulin resistance in the absence of induction of pro-inflammatory cytokines. Insulin resistance by olanzapine was stronger than induced by high concentration of pro-inflammatory cytokines even in combinations, suggesting the contribution of factors other than the classical inflammatory cytokines to promote insulin resistance in adipocytes by olanzapine. Conclusion: Macrophage/adipocyte co-cultures recapitulate the features of olanzapine-induced insulin resistance and implicate the existence of yet unknown factors in mediating this effect.
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- De Groot, C. J., et al.
(författare)
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Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity
- 2021
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 71, s. 653-662
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Tidskriftsartikel (refereegranskat)abstract
- This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated.
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- Chaychenko, T, et al.
(författare)
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Difference in Insulin Resistance Assessment between European Union and Non-European Union Obesity Treatment Centers (ESPE Obesity Working Group Insulin Resistance Project)
- 2021
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 93:11-12, s. 622-633
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The obesity epidemic has become one of the most important public health issues of modern times. Impaired insulin sensitivity seems to be the cornerstone of multiple obesity related comorbidities. However, there is no accepted definition of impaired insulin sensitivity. <b><i>Objective:</i></b> We hypothesize that assessment of insulin resistance differs between centers. <b><i>Methods:</i></b> The ESPE Obesity Working Group (ESPE ObWG) Scientific Committee developed a questionnaire with a focus on the routine practices of assessment of hyperinsulinemia and insulin resistance, which was distributed through Google Docs platform to the clinicians and researchers from the current ESPE ObWG database (<i>n</i> = 73). Sixty-one complete responses (84% response rate) from clinicians and researchers were analyzed: 32 from European Union (EU) centers (representatives of 14 countries) and 29 from Non-EU centers (representatives from 10 countries). Standard statistics were used for the data analysis. <b><i>Results:</i></b> The majority of respondents considered insulin resistance (IR) as a clinical tool (85.2%) rather than a research instrument. For the purpose of IR assessment EU specialists prefer analysis of the oral glucose tolerance test (OGTT) results, whereas non-EU ones mainly use Homeostatic Model Assessment of Insulin Resistance (HOMA-IR; <i>p</i> = 0.032). There was no exact cutoff for the HOMA-IR in either EU or non-EU centers. A variety of OGTT time points and substances measured per local protocol were reported. Clinicians normally analyzed blood glucose (88.52% of centers) and insulin (67.21%, mainly in EU centers, <i>p</i> = 0.0051). Furthermore, most participants (70.5%) considered OGTT insulin levels as a more sensitive parameter of IR than glucose. Meanwhile, approximately two-thirds (63.9%) of the centers did not use any cutoffs for the insulin response to the glucose load. <b><i>Conclusions:</i></b> Since there is no standard for the IR evaluation and uniform accepted indication of performing, an OGTT the assessment of insulin sensitivity varies between EU and non-EU centers. A widely accepted standardized protocol is needed to allow comparison between centers.
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- Fathzadeh, Mohsen, et al.
(författare)
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FAM13A affects body fat distribution and adipocyte function
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution. Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.
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