Researchers at the Advanced Research Unit on Metabolism, Development & Aging (ARUMDA), in the Tata Institute of Fundamental Research (TIFR, Mumbai and TIFR Hyderabad), have unveiled a comprehensive understanding of the harmful effects of sugar-sweetened beverages (SSBs) on human health, using a preclinical mouse model that closely mimics human consumption patterns. The study, published in the Journal of Nutritional Biochemistry, sheds light on how chronic sucrose-water intake (10%) alters key physiological, molecular, and metabolic processes across various organs, driving the onset of diseases such as diabetes and obesity.
Significance of the study
This research provides critical insights into how chronic SSB consumption, even at human-relevant levels, disrupts physiological processes. The study uniquely integrates organ-specific molecular mechanisms, offering a systems-level understanding of how SSBs drive obesity, diabetes, and other metabolic disorders.
Findings from United Nations Public Division and Global Dietary Database, as well as population-level studies conducted by institutes like NHS, NIH and others have clearly indicated an alarming increase in the consumption of sugar sweetened beverages globally, including in India. This makes the findings of the study very relevant as it would contribute to the global efforts in combating the metabolic disorders associated with SSB overconsumption.
Research Methods
The study employed a physiologically relevant model in which mice were provided with 10% sucrose water, mimicking chronic human SSB consumption. Researchers conducted detailed analyses of molecular, cellular, and metabolic responses in multiple tissues, including the liver, muscles and small intestine, under fed and fasted conditions.
Key Findings
The Small Intestine's Central Role in Metabolic Dysregulation
The study discovered that the small intestine is a major contributor to systemic glucose imbalances. Excessive sucrose consumption causes a "molecular addiction" in the intestinal lining, leading to disproportionate absorption of glucose (hexose sugars) over other essential nutrients such as amino acids and fats.
This nutrient uptake imbalance disrupts energy metabolism and amplifies the dysfunction of other organs like the liver and muscles.
Fed and Fasted State Differences
The impact of chronic dietary perturbation affecting physiology differently under fed and fasted states is under-appreciated. In this regard, the study demonstrated distinct anabolic and catabolic responses in fed versus fasted states due to chronic sucrose intake. This imbalance further underscores how nutrient allocation and resource mobilization contribute to systemic metabolic disorders.
Hepatic and Muscular Effects
Despite increased glucose absorption, the liver does not exhibit altered gene expression related to glucose metabolism. Instead, systemic insulin resistance is triggered, exacerbating gluconeogenesis (glucose production by the liver) that leads to metabolic imbalance.
In skeletal muscles, mitochondrial dysfunction and reduced efficiency in glucose utilization further contribute to the impaired metabolic state.
Implications for Public Health
The findings stress the urgent need for policies and awareness campaigns to reduce SSB consumption, particularly among vulnerable populations.
The identification of tissue-specific effects provides a roadmap for developing targeted therapies to combat the rising global burden of metabolic diseases linked to high sugar intake.
Potential Therapeutic Targets
By identifying these tissue-specific mechanisms, researchers propose targeting intestinal nutrient transport pathways and mitochondrial function across tissues as potential strategies to mitigate the metabolic effects of SSB consumption.
Publication: Ganguly, Saptarnab, et al. "Consumption of sucrose-water rewires macronutrient uptake and utilization mechanisms in a tissue specific manner." The Journal of Nutritional Biochemistry (2025): 109850.
