Acylcarnitines in Metabolic Health and Disease in Africa: A Systematic Review of Fatty Acid Oxidation, Insulin Resistance, and Cardiometabolic Risk

Le résumé fourni par la source

Acylcarnitines are a diverse group of metabolites formed through the esterification of carnitine with fatty acids and organic acids. They play a critical role in cellular energy metabolism by facilitating the transport of long-chain fatty acids across the inner mitochondrial membrane for β-oxidation, a process essential for adenosine triphosphate (ATP) production, particularly in metabolically active tissues such as skeletal muscle, liver, and cardiac muscle (Xiang et al., 2025). Beyond their traditional role as intermediates of fatty acid metabolism, acylcarnitines have gained considerable attention as potential biomarkers of metabolic dysfunction due to their close association with mitochondrial activity, substrate utilization, and metabolic flexibility (Xiang et al., 2025). Fatty acid oxidation is a tightly regulated metabolic pathway responsible for maintaining energy homeostasis during fasting and periods of increased energy demand. Under normal physiological conditions, fatty acids are transported into mitochondria via the carnitine shuttle system involving carnitine palmitoyltransferase I (CPT-I), carnitine-acylcarnitine translocase, and CPT-II. Impairments in these pathways can result in incomplete fatty acid oxidation and subsequent accumulation of acylcarnitine species in tissues and circulation (Longo et al., 2016; Peña-Quintana & Correcher-Medina, 2024). Emerging evidence suggests that elevated concentrations of short-, medium-, and long-chain acylcarnitines reflect mitochondrial overload and metabolic inflexibility, both of which are hallmarks of obesity, insulin resistance, and cardiometabolic disease (Aguer et al., 2015; Gander et al., 2021). The burden of metabolic diseases has risen dramatically across Africa over the past two decades. Rapid urbanization, nutritional transitions, reduced physical activity, and population ageing have contributed to increasing rates of obesity, insulin resistance, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease throughout the continent (Issaka et al., 2023; Malema & Frantz, 2025; Nsabimana et al., 2024). Current estimates indicate that more than 24 million adults in Africa are living with diabetes, with projections suggesting this number could more than double by 2045 if current trends continue (Wang et al., 2025). Similarly, obesity prevalence has increased substantially in both urban and rural populations, creating a growing burden of cardiometabolic complications and placing additional strain on already resource-constrained healthcare systems (Ng et al., 2025). Recent metabolomic studies have identified distinct acylcarnitine signatures associated with various metabolic disorders. Elevated circulating branched-chain amino acid-related acylcarnitines and medium-chain acylcarnitines have been consistently linked to insulin resistance and the development of T2DM (Hosseinkhani et al., 2022; Taghizadeh et al., 2023). Likewise, alterations in long-chain acylcarnitine profiles have been reported among individuals with obesity and NAFLD, suggesting impaired mitochondrial fatty acid utilization and hepatic lipid accumulation (Enooku et al., 2019). In cardiovascular disease, particularly heart failure, accumulation of long-chain acylcarnitines has been associated with myocardial metabolic remodeling, impaired cardiac energetics, and adverse clinical outcomes (Ahmad et al., 2016). Despite increasing global research on acylcarnitines, evidence from African populations remains limited. Most metabolomic investigations have been conducted in North America, Europe, and parts of Asia, with relatively few studies examining acylcarnitine profiles among African populations despite the continent’s rapidly increasing burden of metabolic disease. Genetic diversity, environmental exposures, dietary patterns, infectious disease burdens, and socioeconomic factors unique to African populations may influence acylcarnitine metabolism and affect the applicability of findings derived from non-African populations (Chabi et al., 2026). Therefore, this systematic review aims to synthesize current evidence regarding the role of acylcarnitines in metabolic health and disease in Africa, with particular emphasis on fatty acid oxidation, insulin resistance, and cardiometabolic risk.

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