Exploring the link between obesity and hypothyroidism in autoimmune thyroid diseases: a metabolic perspective.

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice.

BACKGROUND: Increasing evidence has linked the thyroid dysfunction to the pathogenesis of dementia. Evidence from clinical studies has demonstrated that hypothyroidism is related to an increased risk of dementia. But the association of hyperthyroidism with dementia is largely unknown. METHODS: We used the adenovirus containing thyrotropin receptor (TSHR) amino acid residues 1-289 (Ad-TSHR289)-induced Graves' disease (GD) phenotype in Alzheimer's disease (AD) model mice (APP/PS1 mice) to evaluate the effect of hyperthyroidism on the cognitive function and ß-amyloid (Aß) accumulation. RESULTS: GD mice exhibited a stable long-term hyperthyroidism and cognitive deficits. Single Cell RNA-sequencing analysis indicated that microglia function played a critical role in the pathophysiological processes in GD mice. Neuroinflammation and polarization of microglia (M1/M2 phenotype) and activated receptor-interacting serine/threonine protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudo-kinase (MLKL)-mediated necroptosis contributed to the pathological process, including Aß deposition and neuronal loss. RIPK3 inhibitor could inhibit GD-mediated Aß accumulation and neuronal loss. CONCLUSIONS: Our findings reveal that GD hyperthyroidism aggravates cognitive deficits in AD mice and induces Aß deposition and neuronal loss by inducing neuroinflammation and RIPK3/MLKL-mediated necroptosis.

The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model.

Background: Previous research has shown a tight relationship between the G0/G1 switch gene 2 (G0S2) and metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and obesity and diabetes, and insulin resistance has been shown as the major risk factor for both NAFLD and T2DM. However, the mechanisms underlying the relationship between G0S2 and insulin resistance remain incompletely understood. Our study aimed to confirm the effect of G0S2 on insulin resistance, and determine whether the insulin resistance in mice fed a high-fat diet (HFD) results from G0S2 elevation. Methods: In this study, we extracted livers from mice that consumed HFD and received tail vein injections of AD-G0S2/Ad-LacZ, and performed a proteomics analysis. Results: Proteomic analysis revealed that there was a total of 125 differentially expressed proteins (DEPs) (56 increased and 69 decreased proteins) among the identified 3583 proteins. Functional enrichment analysis revealed that four insulin signaling pathway-associated proteins were significantly upregulated and five insulin signaling pathway -associated proteins were significantly downregulated. Conclusion: These findings show that the DEPs, which were associated with insulin resistance, are generally consistent with enhanced insulin resistance in G0S2 overexpression mice. Collectively, this study demonstrates that G0S2 may be a potential target gene for the treatment of obesity, NAFLD, and diabetes.