To Boost or to Reset: The Role of Lactoferrin in Energy Metabolism Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Divine Aleru
Researched by:
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Divine Aleru
ID
Divine Aleru
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What Was Reviewed?
The paper is a comprehensive review article that explores lactoferrin (Lf), an iron-binding glycoprotein, and its multifaceted role in human energy metabolism. The authors investigated the molecular and physiological actions of Lf in the modulation of glucose and lipid pathways, its impact on iron and trace metal homeostasis, and its implications for addressing metabolic syndrome, obesity, and related conditions. This review draws from both in vitro and in vivo studies, including human and animal models and integrates findings across disciplines such as immunology, metabolism, and microbiology.
Who Was Reviewed?
The review analyzed a wide range of subjects and experimental models, including human clinical data, animal studies (e.g., rats and mice under high-fat diet or glucose challenge), and cellular models (e.g., HepG2 hepatocytes, adipocytes, intestinal epithelial cells). Special attention was given to individuals with metabolic disorders such as insulin resistance, dyslipidemia, and type 2 diabetes. Pediatric and adult populations, as well as different Lf sources (bovine and camel), were also discussed for their therapeutic relevance.
What Were the Most Important Findings?
Lactoferrin plays a bidirectional role in energy metabolism—either boosting or resetting it depending on the physiological context. It regulates glucose metabolism by enhancing insulin signaling via the IRS-1/PI3K/Akt pathway, upregulating GLUT-4 translocation, and stimulating GLP-1 secretion. In diabetic and stressed animal models, lactoferrin reduced fasting glucose and insulin levels, improved glucose tolerance, and suppressed inflammatory cytokines like IL-6, TNF-α, and IL-1β. These benefits were also observed in pediatric patients with type 2 diabetes who received camel-derived Lf.
On lipid metabolism, lactoferrin modulated adipogenesis by downregulating key pathways such as PPARγ, SREBP-1, and ACC, and decreased serum LDL-C and hepatic lipid accumulation while enhancing HDL-C levels. It exerted these effects partly through activation of AMPK and LRP1-related signaling. Notably, lactoferrin interacted with gut microbiota and bile acids to influence lipid and cholesterol absorption and excretion, suggesting a microbiome-mediated mechanism. Studies showed that Mn- or Zn-bound Lf enhanced Lactobacillus growth, linking it to microbiome modulation.
What Are the Implications of This Review?
This review establishes lactoferrin as a safe, non-toxic, and clinically promising nutraceutical for managing metabolic dysfunctions such as insulin resistance, type 2 diabetes, dyslipidemia, and obesity. Its capacity to influence both host cell signaling and gut microbiota highlights its role as a multitargeted intervention. The dual behavior of Lf—either activating or repressing metabolic pathways depending on the condition—suggests its adaptive potential in both preventive and therapeutic settings. Furthermore, the recognition of Lf’s impact on iron and trace metal balance underscores its broader relevance in inflammatory and infectious disease contexts. Future clinical implementation will require attention to formulation (e.g., apo- vs. holo-Lf), dosage, and patient-specific factors.