Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases.

Brown adipocytes dissipate chemical energy as heat and confer protection against type 2 diabetes and obesity. Nuclear factor I-A (NFIA) is a transcription factor that orchestrates the brown fat gene programme by activating cell type-specific enhancers and facilitating the genomic binding of PPARγ, the master regulator of adipogenesis, to these enhancers. NFIA promotes mitochondrial oxidative phosphorylation and thermogenesis, while reciprocally suppressing adipose tissue inflammation, thereby contributing to the maintenance of glucose and body weight homeostasis in mice.

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021.

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure.

Objective: To estimate the worldwide burden of SAH.

Interaction between type 2 diabetes polygenic risk and physical activity on cardiovascular outcomes.

Aims: The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes.

Overexpression of UBE2E2 in Mouse Pancreatic β-Cells Leads to Glucose Intolerance via Reduction of β-Cell Mass.

Genome-wide association studies have identified several gene polymorphisms, including UBE2E2, associated with type 2 diabetes. Although UBE2E2 is one of the ubiquitin-conjugating enzymes involved in the process of ubiquitin modifications, the pathophysiological roles of UBE2E2 in metabolic dysfunction are not yet understood. Here, we showed upregulated UBE2E2 expression in the islets of a mouse model of diet-induced obesity.

NFIA in adipocytes reciprocally regulates mitochondrial and inflammatory gene program to improve glucose homeostasis.

Adipose tissue is central to regulation of energy homeostasis. Adaptive thermogenesis, which relies on mitochondrial oxidative phosphorylation (Ox-Phos), dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to type 2 diabetes and obesity.

Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator.

The in vitro study of white, brown, and beige adipocyte differentiation enables the investigation of cell-autonomous functions of adipocytes and their mechanisms. Immortalized white preadipocyte cell lines are publicly available and widely used. However, the emergence of beige adipocytes in white adipose tissue in response to external cues is difficult to recapitulate to the full extent using publicly available white adipocyte cell lines.

Chromatin immunoprecipitation with mouse adipocytes using hypotonic buffer to enrich nuclear fraction before fixation.

Chromatin immunoprecipitation (ChIP) experiments with differentiated adipocytes are challenging because lipid droplets interfere with immunoprecipitation efficiency. Here, the author describes optimized procedures to minimize the burden of lipid droplets by using hypotonic buffer to enrich nuclear fraction before formaldehyde crosslinking, thus increasing the sensitivity and specificity of ChIP experiments with differentiated adipocytes. The author also describes steps after fixation, including sonication, immunoprecipitation, washing, reverse-crosslinking, and purification.

NFIA determines the -effect of genetic variation on Ucp1 expression in murine thermogenic adipocytes.

Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling protein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a -regulatory variant rs47238345 that is responsible for differential Ucp1 expression.

FTO Obesity Variant-Exercise Interaction on Changes in Body Weight and BMI: The Taiwan Biobank Study.

Context: Gene-exercise interaction on cross-sectional body mass index (BMI) has been extensively studied and is well established. However, gene-exercise interaction on changes in body weight/BMI remains controversial.

Objective: To examine the interaction between the FTO obesity variant and regular exercise on changes in body weight/BMI.

Deep Neural Network for Reducing the Screening Workload in Systematic Reviews for Clinical Guidelines: Algorithm Validation Study.

Background: Performing systematic reviews is a time-consuming and resource-intensive process.

Objective: We investigated whether a machine learning system could perform systematic reviews more efficiently.

Methods: All systematic reviews and meta-analyses of interventional randomized controlled trials cited in recent clinical guidelines from the American Diabetes Association, American College of Cardiology, American Heart Association (2 guidelines), and American Stroke Association were assessed.

NFIA differentially controls adipogenic and myogenic gene program through distinct pathways to ensure brown and beige adipocyte differentiation.

The transcription factor nuclear factor I-A (NFIA) is a regulator of brown adipocyte differentiation. Here we show that the C-terminal 17 amino acid residues of NFIA (which we call pro#3 domain) are required for the transcriptional activity of NFIA. Full-length NFIA-but not deletion mutant lacking pro#3 domain-rescued impaired expression of PPARγ, the master transcriptional regulator of adipogenesis and impaired adipocyte differentiation in NFIA-knockout cells.

NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program.

Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers.

Polyarteritis nodosa diagnosed by surgically resected jejunal necrosis following acute abdomen.

The differential diagnosis of acute abdomen is typically extremely broad in range, with vasculitis posing a rare but potentially life-threatening cause of acute abdomen. Here, we report a case of acute abdomen with bowel wall thickening limited to jejunum, accompanied by unexplained renal dysfunction. Later, the patient was diagnosed as having polyarteritis nodosa based on surgically resected jejunal necrosis.