‘Obesities’: Position statement on a complex disease entity with multifaceted drivers

Yárnoz-Esquíroz, Patricia; Olazarán, Laura; Aguas-Ayesa, Maite; Perdomo, Carolina M; García‐Goñi, Marta; Silva, Camilo; Fernández-Formoso, José Antonio; Escalada, Javier; Montecucco, Fabrizio; Portincasa, Piero; Frühbeck, Gema

doi:10.1111/eci.13811

Cited by 26 publications

(20 citation statements)

References 46 publications

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“…Obesity constitutes one of the most prevalent diseases reaching epidemic proportions and is becoming a leading global health threat [ 1 , 2 ]. Excess adipose tissue (AT) prompts not only physical and mental impairment, but also increased risk of developing non-communicable comorbidities, including cardiovascular diseases, insulin resistance (IR), type 2 diabetes (T2D), respiratory failure, reduced fertility, and certain types of cancers, therefore shortening lifespans [ 3 , 4 ]. AT-chronic inflammation constitutes a key factor in the onset and progression of obesity-associated metabolic alterations, with the infiltration of monocytes from the bloodstream contributing to its dysregulation and favoring local and systemic inflammation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance

et al. 2022

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Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.

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Section: Introductionmentioning

confidence: 99%

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance

et al. 2022

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“…However, even when a metabolically healthy obese phenotype can be maintained over a long period of time, obesity remains a risk factor for cardiovascular disease [ 37 ]. It is a well-known phenomenon that responses to treatment are heterogeneous, which, in line with the existence of diverse obesities [ 38 ], may influence long-term outcomes following weight loss [ 39 ]. Our data are in agreement with the Look AHEAD study that examined the effects of lifestyle intervention in a large cohort of participants with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

The Extent of Lifestyle-Induced Weight Loss Determines the Risk of Prediabetes and Metabolic Syndrome Recurrence during a 5-Year Follow-Up

Zimmermann

Vogel²,

Mathew

et al. 2022

Nutrients

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It is controversial whether lifestyle-induced weight loss (LIWL) intervention provides long-term benefit. Here, we investigated whether the degree of weight loss (WL) in a controlled LIWL intervention study determined the risk of prediabetes and recurrence of metabolic syndrome (MetS) during a 5-year follow-up. Following LIWL, 58 male participants (age 45–55 years) were divided into four quartiles based on initial WL: Q1 (WL 0–8.1%, n = 15), Q2 (WL 8.1–12.8%, n = 14), Q3 (WL 12.8–16.0%, n = 14), and Q4 (WL 16.0–27.5%, n = 15). We analyzed changes in BMI, HDL cholesterol, triglycerides (TGs), blood pressure, and fasting plasma glucose (FPG) at annual follow-up visits. With a weight gain after LIWL between 1.2 (Q2) and 2.5 kg/year (Q4), the reduction in BMI was maintained for 4 (Q2, p = 0.03) or 5 (Q3, p = 0.03; Q4, p < 0.01) years, respectively, and an increase in FPG levels above baseline values was prevented in Q2–Q4. Accordingly, there was no increase in prediabetes incidence after LIWL in participants in Q2 (up to 2 years), Q3 and Q4 (up to 5 years). A sustained reduction in MetS was maintained in Q4 during the 5-year follow-up. The present data indicate that a greater initial LIWL reduces the risk of prediabetes and recurrence of MetS for up to 5 years.

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“…Obesity, a current global pandemic, is considered a preventable risk factor for CC development [ 27 , 28 , 29 , 30 ]; moreover, a worse cancer prognosis has been described among patients with fat excess [ 27 , 31 ]. Increasing evidence reveals that obesity prompts the development of CC through the pathophysiological effects of VAT that favours tumourigenesis, tumour growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins

Domench

Gómez-Ambrosi

Ramírez

et al. 2022

IJMS

Self Cite

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Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-α and TGF-β), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.

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‘Obesities’: Position statement on a complex disease entity with multifaceted drivers

Cited by 26 publications

References 46 publications

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance

The Extent of Lifestyle-Induced Weight Loss Determines the Risk of Prediabetes and Metabolic Syndrome Recurrence during a 5-Year Follow-Up

Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins

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