NF-κB, inflammation and metabolic disease. Metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis have traditionally been viewed as lipid storage disorders caused by overnutrition. However, chronic low-grade inflammation is now recognized as a key factor in the initiation, progression, and development of these diseases. NF-κB, a key transcription factor in inflammation, has been implicated in the development of these diseases, reinforcing inflammation's role in their etiology and offering new therapeutic approaches. Inflammation is a critical physiological challenge, balancing immune response and energy metabolism. In modern times, overnutrition has led to metabolic diseases being the leading cause of death in the US, with rising incidence globally. Inflammation, once a protective mechanism, can now contribute to diseases like allergy, asthma, diabetes, and cancer. Metabolic syndrome involves conditions like obesity, insulin resistance, and atherosclerosis, affecting a quarter of American adults and over a million children. These diseases are interconnected, with obese individuals at higher risk for type 2 diabetes and insulin-resistant individuals for cardiovascular diseases. This review examines the role of inflammatory signaling pathways in metabolic diseases, focusing on NF-κB, a central regulator of inflammation. NF-κB directs inflammatory responses by controlling gene expression involved in inflammation. It is activated by cytokines and pathogen-associated molecular patterns, leading to the expression of genes that mediate cell proliferation and immune activation. NF-κB is not limited to hematopoietic cells but is active in most cell types, including the liver, adipose tissue, and central nervous system. In macrophages, inflammation begins with the recognition of PAMPs, leading to the release of cytokines that activate NF-κB. Activated macrophages produce antimicrobial molecules and chemokines, aiding in pathogen clearance. The IKK complex regulates NF-κB activation, with IKKβ and NEMO being essential for inflammatory and immune responses. NF-κB regulates inflammation through cytokine-directed cell differentiation, influencing macrophage types (M1 and M2). M1 macrophages produce pro-inflammatory cytokines, while M2 macrophages secrete anti-inflammatory cytokines. NF-κB's role in macrophage differentiation is critical in inflammatory metabolic diseases. Inflammation in obese adipose tissue is marked by chronic activation of inflammatory pathways, with adipocytes producing pro-inflammatory cytokines. This leads to the recruitment of monocytes and the differentiation of M1 macrophages, contributing to systemic inflammation. T-cells and M1 macrophages are associated with chronic inflammation in metabolic diseases. NF-κB's role in obesity is supported by studies showing its involvement in the development of metabolic diseases in genetic mouse models. Obesity is linked to chronic inflammation, with adipose tissue macrophages playing a key role. TLRs and gut microbiota also contribute to obesity through inflammatory pathways. Inflammation in theNF-κB, inflammation and metabolic disease. Metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis have traditionally been viewed as lipid storage disorders caused by overnutrition. However, chronic low-grade inflammation is now recognized as a key factor in the initiation, progression, and development of these diseases. NF-κB, a key transcription factor in inflammation, has been implicated in the development of these diseases, reinforcing inflammation's role in their etiology and offering new therapeutic approaches. Inflammation is a critical physiological challenge, balancing immune response and energy metabolism. In modern times, overnutrition has led to metabolic diseases being the leading cause of death in the US, with rising incidence globally. Inflammation, once a protective mechanism, can now contribute to diseases like allergy, asthma, diabetes, and cancer. Metabolic syndrome involves conditions like obesity, insulin resistance, and atherosclerosis, affecting a quarter of American adults and over a million children. These diseases are interconnected, with obese individuals at higher risk for type 2 diabetes and insulin-resistant individuals for cardiovascular diseases. This review examines the role of inflammatory signaling pathways in metabolic diseases, focusing on NF-κB, a central regulator of inflammation. NF-κB directs inflammatory responses by controlling gene expression involved in inflammation. It is activated by cytokines and pathogen-associated molecular patterns, leading to the expression of genes that mediate cell proliferation and immune activation. NF-κB is not limited to hematopoietic cells but is active in most cell types, including the liver, adipose tissue, and central nervous system. In macrophages, inflammation begins with the recognition of PAMPs, leading to the release of cytokines that activate NF-κB. Activated macrophages produce antimicrobial molecules and chemokines, aiding in pathogen clearance. The IKK complex regulates NF-κB activation, with IKKβ and NEMO being essential for inflammatory and immune responses. NF-κB regulates inflammation through cytokine-directed cell differentiation, influencing macrophage types (M1 and M2). M1 macrophages produce pro-inflammatory cytokines, while M2 macrophages secrete anti-inflammatory cytokines. NF-κB's role in macrophage differentiation is critical in inflammatory metabolic diseases. Inflammation in obese adipose tissue is marked by chronic activation of inflammatory pathways, with adipocytes producing pro-inflammatory cytokines. This leads to the recruitment of monocytes and the differentiation of M1 macrophages, contributing to systemic inflammation. T-cells and M1 macrophages are associated with chronic inflammation in metabolic diseases. NF-κB's role in obesity is supported by studies showing its involvement in the development of metabolic diseases in genetic mouse models. Obesity is linked to chronic inflammation, with adipose tissue macrophages playing a key role. TLRs and gut microbiota also contribute to obesity through inflammatory pathways. Inflammation in the