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#87 - Rick Johnson, M.D.: Fructose—The common link in high blood pressure, insulin resistance, T2D, & obesity?

The Peter Attia Drive

NOTE

The Fat Switch

Adenosine triphosphate (ATP) depletion initiates a critical biochemical process that influences fat storage and energy expenditure. When ATP levels drop, intracellular phosphate levels also decrease, activating the enzyme AMP deaminase (AMPD), which converts adenosine monophosphate (AMP) into uric acid. This shift triggers a pathway associated with insulin resistance, fatty liver, elevated blood pressure, and obesity, particularly from sugar intake. AMP stands at a metabolic crossroads, offering two divergent pathways: the AMP-activated protein kinase (AMPK) pathway, which promotes fat burning and energy production, and the AMP deaminase (AMPD) pathway, driving fat storage and insulin resistance. The metabolic consequences hinge on this choice; stimulating AMPK yields beneficial effects, while AMPD activation leads to negative health outcomes. The essential factor in guiding this switch is falling intracellular phosphate levels, influenced by fructose metabolism, which sequesters phosphate and exacerbates the metabolic issues associated with obesity and diabetes.

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