The role of Wnt pathway in obesity induced inflammation and diabetes: a review

Das, Biswajit; Das, Manas; Kalita, Anuradha; Baro, Momita Rani

doi:10.1007/s40200-021-00862-8

Cited by 9 publications

(5 citation statements)

References 158 publications

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“…Hence, we found decreased expression of WNT5A in SAT in diabetic patients and reduced expression of WNT5A in VAT in metabolic syndrome patients. In this sense, although WNT5A has lipogenic effects, it has been reported that the inhibition of its pathway in the pancreas can lead to diabetes [ 69 ], which agrees with our results. Conversely, noncanonical WNT5A signaling has been found to play an essential role in obesity-induced VAT inflammation and metabolic dysfunction, which can promote insulin resistance under conditions of overfeeding [ 28 , 48 , 72 ].…”

Section: Discussionsupporting

confidence: 93%

“…Still, the increased expression of WNT5A in adipose tissue would make sense in firsts stages of steatosis, since in subjects with MO, there is an adipose tissue overproliferation mediated by WNT5A [ 54 ]. This excessive proliferation gives rise to a saturation of the adipose tissue depots that reduce insulin sensitivity [ 68 , 69 ]. In this regard, insulin resistance may impact the liver inducing hepatic steatosis [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

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Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

Bertran

Portillo-Carrasquer

Barrientos-Riosalido

et al. 2022

IJMS

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Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

Bertran

Portillo-Carrasquer

Barrientos-Riosalido

et al. 2022

IJMS

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“…The Wnt/β-catenin pathway influences insulin action and systemic glucose homeostasis. 252 , 253 The canonical Wnt transcriptional effector TCF7L2 was found to be closely related to susceptibility to T2D. 254 In visceral adipose tissues of patients with obesity-related diabetes and HDF-fed mice, the Wnt/β-catenin pathway is downregulated.…”

Section: Signaling Pathways In the Pathogenesis Of Obesitymentioning

confidence: 99%

Signaling pathways in obesity: mechanisms and therapeutic interventions

Wen

Zhang

et al. 2022

Sig Transduct Target Ther

182

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Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. Although lifestyle intervention (diet and exercise) has remarkable effects on weight management, achieving long-term success at weight loss is extremely challenging, and the prevalence of obesity continues to rise worldwide. Over the past decades, the pathophysiology of obesity has been extensively investigated, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. In this review, we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies, focusing on signaling pathways and their roles in the regulation of food intake, glucose homeostasis, adipogenesis, thermogenesis, and chronic inflammation. We also discuss the current anti-obesity drugs, as well as weight loss compounds in clinical trials, that target these signals. The evolving knowledge of signaling transduction may shed light on the future direction of obesity research, as we move into a new era of precision medicine.

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“…AXIN1 is a negative regulator of the Wnt/β-catenin signaling pathway (Kikuchi, 1999). This pathway is increasingly recognized to play an important role in inflammatory diseases, diabetes and cancer (Das, Das, Kalita, & Baro, 2021; Jridi, Canté-Barrett, Pike-Overzet, & Staal, 2021). Conversely, CDCP1 (CUB domain-containing protein 1), a transmembrane receptor that is a Wnt signaling promoter (He et al, 2020) was significantly up-regulated (log 2 FC 0.7; P =1.8 x 10 -61 ) in the Tanzanian cohort, suggesting enhanced activity of the Wnt/β-catenin signaling pathway in the Tanzanian participants.…”

Section: Resultsmentioning

confidence: 99%

Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors

Temba

Vadaq

Kullaya

et al. 2022

Preprint

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Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characterstics of an urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/β-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition in the NCDs epidemic in sub-Saharan Africa and the inclusion of underrepresented populations in systems immunology studies.

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The role of Wnt pathway in obesity induced inflammation and diabetes: a review

Cited by 9 publications

References 158 publications

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

Signaling pathways in obesity: mechanisms and therapeutic interventions

Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors

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