The contribution of type 2 diabetes mellitus to hypothalamic inflammation and depressive disorders in young patients with obesity

Dong, Guanzhong; Zhang, Qiaoyang; Jiao, Yuwen; Ma, Yi; Zhu, Shumin; Zhang, Li-Hao; Zhang, Min; Chen, Yun; Ye, Xinhua; Cao, Yin; Tang, Liming

doi:10.21037/atm-22-192

Cited by 5 publications

(6 citation statements)

References 29 publications

(24 reference statements)

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“…More than ½ of patients with type 2 diabetes mellitus having obstructive sleep apnea [ 60 ], with sleep apnea contributing to weight gain and visceral fat accumulation [ [61] , [62] , [63] ]. Diabetes-related inflammation are interrelated with obesity [ 64 ], with diabetes being potentially associated with hypothalamic inflammation [ 65 ], which in turn is also linked to promoting obesity [ 66 , 67 ]. Diabetes-related eye disease [ 68 ] , kidney disease [ 69 ] , and skin disease (i.e., diabetes foot ulcer) [ 70 ] may impair physical activity, thus potentially impair weight reduction effectiveness.…”

Section: Potential Mechanisms For Impaired Weight Reduction Among Pat...mentioning

confidence: 99%

Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review

Bays

2023

Obesity Pillars

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Section: Potential Mechanisms For Impaired Weight Reduction Among Pat...mentioning

confidence: 99%

Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review

Bays

2023

Obesity Pillars

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“…With the continuous improvements in the quality of life of the population, it is expected that there will be more than one billion people with diabetes globally by 2030, and more than 90 million patients will have diabetic retinopathy (4). The development of diabetes is closely related to the inflammatory response (5). Researchers have found increased levels of inflammatory factors such as interleukin-1β (IL-1β) and interleukin-6 (IL-6) in aqueous humor and serum of patients with diabetic retinopathy.…”

Section: Introductionmentioning

confidence: 99%

Gambogic acid affects high glucose-induced apoptosis and inflammation of retinal endothelial cells through the NOX4/NLRP3 pathway

Ye¹,

Feng²,

Hu³

2023

Ann Transl Med

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Background: This study aimed to investigate the effect and mechanism of gambogic acid (GA) on the apoptosis and inflammation of human retinal endothelial cells (HRECs) under high glucose conditions. Methods: HRECs were cultured in a high glucose medium to simulate retinal endothelial cell injury induced by diabetic retinopathy. Flow cytometry was used to analyze the apoptosis level of HRECs. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Western blotting was applied to detect the intracellular apoptosis-related proteins and expression levels of NADPH oxidase 4 (NOX4), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin (IL)-1β. Enzyme linked immunosorbent assay (ELISA) was utilized to detect the expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) in the cell supernatants. The messenger RNA (mRNA) levels of IL-6, IL-8, IL-10, and TNF-α were detected by reverse transcription-polymerase chain reaction (RT-qPCR). Results:We observed that high glucose induced the apoptosis and inflammation of HRECs. In addition, the high glucose environment promoted NOX/NLRP3 pathway activation. The activity of HRECs was not significantly affected by the presence of 20 μM or less of GA, and 15 μM of GA could restore the diminished activity of HRECs induced by high glucose. The apoptosis of HRECs cultured under high glucose conditions was significantly inhibited (P<0.05), the levels of IL-6, IL-8, and TNF-α in the cell supernatant were significantly decreased (P<0.05), and the levels of IL-10 were significantly increased (P<0.05). Meanwhile, the relative mRNA expression levels of IL-6, IL-8, and TNF-α in HRECs were significantly decreased (P<0.05), while those of IL-10 were significantly increased (P<0.05). The activity of the high glucose-induced NOX4/NLRP3 pathway in HRECs was significantly inhibited after treatment with 15 μM of GA (P<0.05). Following activation of the NOX4/NLRP3 pathway in HRECs, the apoptosis level was significantly increased (P<0.05), and the inflammatory response was aggravated (P<0.05). Inhibiting the activity of the intracellular NOX4/NLRP3 pathway markedly inhibited cell apoptosis and the inflammatory response (P<0.05).Conclusions: GA can inhibit the apoptosis and inflammation of HRECs under high glucose conditions by inhibiting the activity of the NOX4/NLRP3 pathway. This has a significant inhibitory effect on diabetic retinopathy, which is worthy of further study.

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“…A recent study showed that elevated FBG was an independent predictor of depressive disorder in young patients with obesity. 31 And we further found that higher FBG level was associated with a higher risk of depression in T2DM patients (OR: 1.06, 95% CI: 1.00–1.11).…”

Section: Discussionmentioning

confidence: 51%

HTR1A Gene Polymorphism in Type 2 Diabetes Mellitus Comorbid with Major Depressive Disorder in a Chinese Population

Simayi¹,

Guan²

2022

DMSO

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Background Major depressive disorder is a frequent mental illness, which is common in patients with type 2 diabetes. Type 2 diabetes comorbid with depression has a worse prognosis. There are multiple risk factors for depression, and genetic studies have shown that gene polymorphism may play an important role in the pathogenesis of depression. Methods A total of 874 patients with type 2 diabetes were recruited for this study and divided into two groups: depressive group (DDM group, n = 234) and non-depressive group (NDDM group, n = 640). HTR1A gene polymorphisms (rs6295, rs878567, rs1800044) genotyping work was performed using a custom by design 48-Plex SNPscan TM Kit. Results The rs6295, rs878567, and rs1800044 SNPs were not associated with type 2 diabetes comorbid with depression. Female sex, age, and FBG level increased the risk of depression in patients with type 2 diabetes. Conclusion HTR1A rs6295, rs878567, and rs1800044 SNPs polymorphism is not associated with type 2 diabetes comorbid with depression. Rather, female sex, age, and FBG level are risk factors for depression among patients with type 2 diabetes. Larger studies are needed to further confirm our findings.

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The contribution of type 2 diabetes mellitus to hypothalamic inflammation and depressive disorders in young patients with obesity

Cited by 5 publications

References 29 publications

Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review

Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review

Gambogic acid affects high glucose-induced apoptosis and inflammation of retinal endothelial cells through the NOX4/NLRP3 pathway

HTR1A Gene Polymorphism in Type 2 Diabetes Mellitus Comorbid with Major Depressive Disorder in a Chinese Population

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