Commentary - (2025) Volume 16, Issue 5
AMP-activated protein kinase (AMPK) plays a critical role as a central coordinator of cellular and whole-body metabolism. It senses energy stress, activating catabolic pathways and suppressing anabolic processes to restore ATP homeostasis. AMPK's involvement spans diverse metabolic states, including exercise, nutrient deprivation, and conditions such as type 2 diabetes and cancer. Understanding its mechanisms provides therapeutic avenues for metabolic diseases[1].
Circadian rhythms profoundly influence liver metabolism, impacting glucose, lipid, and amino acid homeostasis. Molecular clock components drive these rhythms, and their disruption leads to metabolic disorders like fatty liver disease, insulin resistance, and obesity. Chronotherapy, aligning treatments with the body's natural rhythms, holds potential to improve metabolic health and manage related diseases[2].
Mitochondria are indispensable for regulating cellular metabolism beyond ATP production, integrating nutrient sensing and signal transduction to influence various metabolic pathways. Mitochondrial dysfunction is implicated in a wide array of metabolic diseases, including obesity, diabetes, and neurodegeneration. Targeting mitochondrial health could be a promising therapeutic strategy[3].
The gut microbiome profoundly impacts host metabolic regulation. Gut bacteria influence energy harvest, nutrient absorption, and produce metabolites like short-chain fatty acids that signal to host tissues. Dysbiosis in the gut microbiome links to metabolic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, making it a key therapeutic target[4].
Cancer cells rewire their metabolism and exploit nutrient sensing pathways to support rapid proliferation and survival. Oncogenic mutations hijack metabolic programs, altering glucose, lipid, and amino acid metabolism. Key nutrient sensors like mTOR and AMPK play roles here. Targeting these pathways and metabolic dependencies offers promising avenues for novel cancer therapies[5].
Adipose tissue macrophages (ATMs) are crucial for metabolic homeostasis, with involvement in metabolic disease development. ATMs respond to nutrient availability and inflammation within adipose tissue, modulating insulin sensitivity, thermogenesis, and lipid metabolism. Dysfunctional ATMs significantly contribute to obesity-induced insulin resistance, offering insights into potential therapeutic targets for metabolic disorders[6].
Exercise profoundly benefits metabolic health through molecular mechanisms. Physical activity induces adaptations in skeletal muscle, liver, and adipose tissue, enhancing glucose uptake, improving insulin sensitivity, and promoting mitochondrial biogenesis. These cellular and systemic changes prevent and manage metabolic diseases, providing a mechanistic basis for exercise as a powerful therapeutic intervention[7].
Epigenetic modifications intricately relate to metabolic reprogramming in cancer progression. Alterations in DNA methylation, histone modifications, and non-coding RNAs influence the expression of metabolic enzymes and transporters, driving the Warburg effect and other hallmarks of cancer metabolism. Targeting these epigenetic regulators could offer new therapeutic strategies to disrupt cancer cell metabolism and inhibit tumor growth[8].
A complex hormonal network governs energy metabolism, specifically the interplay between adipokines from adipose tissue and gut hormones. These endocrine signals communicate between organs to regulate appetite, satiety, glucose homeostasis, and lipid metabolism. Dysregulation in these hormonal pathways contributes to metabolic disorders like obesity and type 2 diabetes, making them crucial therapeutic targets[9].
Dysregulation of brain metabolism plays a critical role in neurodegenerative diseases like Alzheimer's and Parkinson's. Impaired glucose utilization, mitochondrial dysfunction, altered lipid metabolism, and oxidative stress contribute to neuronal vulnerability and neurodegeneration. Exploring therapeutic strategies aimed at restoring metabolic homeostasis in the brain could mitigate disease progression[10].
Cellular and whole-body metabolism is coordinated by intricate mechanisms involving key regulators and external factors. AMP-activated protein kinase (AMPK), for instance, acts as a central energy sensor, responding to stress by adjusting catabolic and anabolic pathways to maintain ATP balance. This ensures cellular energy demands are met, highlighting its fundamental role in metabolic regulation across various physiological states, including exercise and nutrient deprivation. Beyond individual cellular components, broader systemic influences like circadian rhythms profoundly impact liver metabolism, affecting glucose, lipid, and amino acid homeostasis. Disruption of these natural rhythms is directly linked to the development of metabolic disorders such as fatty liver disease, insulin resistance, and obesity, suggesting that aligning treatments with these biological clocks could offer significant health benefits.
Mitochondria are critical beyond their well-known role in ATP production. They actively integrate nutrient sensing and signal transduction, influencing a wide array of metabolic pathways and cellular functions. Dysfunction in mitochondria is a pervasive factor in numerous metabolic diseases, including obesity, diabetes, and even neurodegeneration, positioning mitochondrial health as a promising area for therapeutic interventions. Moreover, the gut microbiome plays an undeniable role as a key regulator of host metabolism. Gut bacteria influence energy harvesting, nutrient absorption, and the production of crucial metabolites like short-chain fatty acids that communicate with host tissues. Imbalances in the gut microbiome, known as dysbiosis, are implicated in the pathogenesis of conditions such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, pointing to the microbiota as a significant therapeutic target.
Metabolic dysregulation is a central feature in various disease states, particularly in cancer. Cancer cells exhibit metabolic rewiring, exploiting nutrient sensing pathways for rapid proliferation and survival. Oncogenic mutations can hijack normal metabolic programs, leading to altered glucose, lipid, and amino acid metabolism. Nutrient sensors like mTOR and AMPK are pivotal in this context, and targeting these pathways represents a promising strategy for novel cancer therapies. Complementing this, epigenetic modificationsâ??alterations in DNA methylation, histone modifications, and non-coding RNAsâ??also profoundly influence metabolic reprogramming in cancer, driving characteristic features like the Warburg effect. Intervening with these epigenetic regulators offers further avenues to disrupt cancer cell metabolism and inhibit tumor growth.
Beyond cancer, other tissues and systems demonstrate crucial metabolic roles. Adipose tissue macrophages (ATMs) are vital for maintaining metabolic homeostasis, responding to nutrient availability and inflammation to modulate insulin sensitivity, thermogenesis, and lipid metabolism. Dysfunctional ATMs are significant contributors to obesity-induced insulin resistance. The brain also faces unique metabolic challenges; dysregulation of brain metabolism is critical in neurodegenerative diseases like Alzheimer's and Parkinson's, involving impaired glucose utilization, mitochondrial dysfunction, altered lipid metabolism, and oxidative stress. Restoring metabolic homeostasis in the brain holds potential to mitigate disease progression. Furthermore, a complex hormonal network, including adipokines and gut hormones, governs energy metabolism, regulating appetite, satiety, glucose homeostasis, and lipid metabolism. Dysregulation in these hormonal pathways contributes to obesity and type 2 diabetes, identifying them as crucial therapeutic targets.
In light of these intricate metabolic connections, exercise emerges as a powerful therapeutic intervention. Physical activity induces beneficial adaptations in skeletal muscle, liver, and adipose tissue, enhancing glucose uptake, improving insulin sensitivity, and promoting mitochondrial biogenesis. These cellular and systemic changes contribute significantly to the prevention and management of a broad spectrum of metabolic diseases. Understanding these diverse molecular mechanisms, from cellular sensors to systemic hormonal and microbial influences, offers a comprehensive framework for developing targeted therapeutic strategies aimed at restoring metabolic health and combating disease.
Metabolism is a finely tuned process regulated by various internal and external factors crucial for health. Central to this are energy sensors like AMP-activated protein kinase (AMPK), which coordinates cellular and whole-body metabolism by responding to energy stress. Circadian rhythms also significantly influence liver metabolism, with their disruption leading to metabolic disorders. Mitochondria, beyond ATP production, integrate nutrient sensing, and their dysfunction is implicated in numerous diseases including obesity and neurodegeneration. The gut microbiome is a profound regulator, influencing nutrient absorption and energy harvest, and its dysbiosis links directly to metabolic diseases. Cancer cells exhibit significant metabolic rewiring, exploiting nutrient sensing pathways for proliferation, while epigenetic modifications further drive cancer metabolism. Adipose tissue macrophages and a complex hormonal network, including adipokines and gut hormones, also play critical roles in metabolic homeostasis, with their dysregulation contributing to diseases like obesity and type 2 diabetes. Importantly, exercise induces beneficial adaptations across tissues, improving metabolic health and serving as a key therapeutic intervention. Understanding these diverse mechanisms offers pathways for addressing a wide array of metabolic and neurodegenerative diseases.
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Indexed at, Google Scholar, Crossref
Received: 01-May-2025, Manuscript No. jdm-25-38710; Editor assigned: 03-May-2025, Pre QC No. jdm-25-38710(PQ); Reviewed: 17-May-2025, QC No. jdm-25-38710; Revised: 22-May-2025, Manuscript No. jdm-25-38710(R); Published: 29-May-2025
Copyright: 2025 Sofia N. Calderon. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
