Insulin Resistance, Dopamine Disruption & MASLD

A Four-Stage Metabolic Cascade — Phase One Is The Root Cause

Dopamine & Serotonin Depletion — Depression, Anxiety or Low Mood

Not a character issue — a direct metabolic outcome. Depending on constitution: depression, anxiety, fatigue or chronic low motivation.

↓ Tyrosine Hydroxylase IDO → Kynurenine Pathway Brain Reward Circuit Impaired ↓ Dopamine & Serotonin

PHASE FOUR

TNF-α & IL-6 cross the blood-brain barrier → suppress neurotransmitter synthesis

MASLD — Metabolic Fatty Liver Disease

Fat-laden liver cells release TNF-α and IL-6 into systemic circulation. Gut dysbiosis reduces dopamine and serotonin precursors. The liver loses its capacity to regulate neurochemical substrates and clear inflammatory mediators.

TNF-α & IL-6 Elevation Gut Dysbiosis ↓ Neurotransmitter Precursors Oxidative Stress

PHASE THREE

Liver fat accumulation → oxidative stress → chronic low-grade systemic inflammation

Hypertension & Hepatic Fat Accumulation

Kidneys — remaining insulin-sensitive — aggressively retain sodium, raising blood pressure. Hyperinsulinaemia simultaneously drives the liver to convert glucose into fat (de novo lipogenesis). Fat builds in liver cells. Autophagy and cellular repair are suppressed.

Renal Sodium Retention RAAS Activation De Novo Lipogenesis Elevated Blood Pressure

PHASE TWO

Kidneys retain sodium → fluid volume rises → blood pressure increases & liver accumulates fat

PHASE ONE — Insulin Resistance: The Root Cause

Cells stop responding to insulin. The body acts as if feeding is continuous and storage is always needed — retaining sodium and water. Only the kidneys and liver remain fully insulin-sensitive, bearing the entire metabolic burden of this hidden dysfunction.

Elevated Fasting Insulin HOMA-IR ≥ 1.9 Pancreatic Overcompensation Silent — Often Undetected For Years