Historically, microglial activation has been associated with diseases of a neurodegenerative and neuroinflammatory nature. Some, like Alzheimer’s disease, Parkinson’s disease, and multiple system atrophy, have been explored extensively, while others pertaining to metabolism not so much. However, emerging evidence points to hypothalamic inflammation mediated by microglia as a driver of metabolic dysregulations, particularly insulin resistance and type 2 diabetes mellitus. Here, we explore this connection further and examine pathways that underlie this relationship, including the IKKβ/NF-κβ, IRS-1/PI3K/Akt, mTOR-S6 Kinase, JAK/STAT, and PPAR-γ signaling pathways. We also investigate the role of non-coding RNAs, namely microRNAs and long non-coding RNAs, in insulin resistance related to neuroinflammation and their diagnostic and therapeutic potential. Finally, we explore therapeutics further, searching for both pharmacological and non-pharmacological interventions that can help mitigate microglial activation.

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities such as hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently accompanied by metabolic disturbances such as insulin resistance, obesity and dyslipidemia. Genome-wide association studies (GWASs) have identified several susceptibility loci, yet little is known about their functional implications. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a powerful gene editing tool in bridging this gap by allowing researchers to directly target candidate genes in ovarian and metabolic pathways. For instance, experimental models have highlighted the role of CYP17A1 and DENND1A.V2 in androgen excess, anti-Müllerian hormone (AMH) in follicular arrest, and insulin receptor substrate 1 (IRS1) and PPARγ in insulin signaling and adipogenesis. To highlight the multifactorial nature of PCOS, animal models, including zebrafish and rodents, have been used to reveal interactions between reproductive and metabolic phenotypes. Nevertheless, most studies remain restricted to single-gene models, and dual-gene models or combined gene editing and hormonal induction models remain underexplored. Future research integrating precision editing, multi-omic platforms, and patient-derived organoids may provide more accurate disease models and novel therapeutic strategies.

Background: The Middle East and North Africa (MENA) region faces a high cardiovascular disease (CVD) burden alongside endemic serum 25(OH)D (vitamin D) deficiency. This systematic review examines the relationship between vitamin D deficiency and CVD risk factors in MENA populations. Methods: PubMed, Cochrane Library, and Scopus were searched from inception to 18 October 2024, for observational studies in the MENA region examining vitamin D deficiency and cardiovascular risk factors in adults. Independent data extraction was conducted. Study quality was appraised using the Joanna Briggs Institute tool and the Newcastle–Ottawa Scale, with risk of bias visualized using Robvis. Weighted mean differences in cholesterol, body mass index (BMI), and HbA1c between those with and without vitamin D deficiency were computed with random-effects meta-analysis. The protocol was registered in PROSPERO (ID: CRD42025615188) and funded by the Royal College of Surgeons in Ireland—Medical University of Bahrain. Results: Seventeen studies from nine MENA countries were included, predominantly cross-sectional, involving community-based and disease-specific cohorts. Vitamin D deficiency was highly prevalent and consistently associated with higher adiposity and central obesity. Several studies reported significant links between deficiency and poor glycemic control, particularly in obese and prediabetic groups. Meta-analysis demonstrated significantly higher total cholesterol (MD = 0.32; 95% CI = 0.11 to 0.52, p < 0.001), BMI (MD = 1.81; 95% CI = 0.68 to 2.94, p < 0.001), and HbA1c levels (MD = 0.31; 95% CI = 0.06 to 0.57, p = 0.02) in vitamin D deficient individuals, with notable heterogeneity. Conclusions: Vitamin D deficiency is highly prevalent in the MENA region and consistently associated with adiposity-related risk factors. Despite heterogeneity, findings underscore the need for public health strategies and further research to clarify causal pathways and population-specific interventions.