What Is It Like to Feel, 'I Have Energy'? Interoception, AMPK vs. mTORC1 & The Biology of Vitality

The Enigma of Subjective Vitality

In his monograph What Is It Like to Feel, "I Have Energy"?, Dr. Fenton LeBon explores one of the most familiar yet scientifically unmapped questions in human biology: What biological information does the brain perceive when an individual states, "I feel energized"?

Dr. LeBon begins by isolating three distinct components: 1. The Conscious Individual: The subject experiencing awareness. 2. The Perceived State of Energy Itself: The biological information being transmitted from the periphery to the central nervous system. 3. The Emotional Response to That State: Feelings of happiness, frustration, or anxiety resulting from the energetic state.

Why Subjective Energy Is Not Just Arousal or Capacity

- It is not physical capacity: A person does not need to lift weights or test VO2 max to know if they feel vital. The sensation exists prior to physical execution. - It is not catecholamine wakefulness: An adrenaline spike causes tachycardia and agitation, but true cellular energy can be experienced in a state of profound physiological tranquility and parasympathetic ease. Conversely, an individual can be wide awake at 3:00 PM while feeling completely depleted.

The Proposed Molecular Sensors: AMPK and mTORC1

Dr. LeBon proposes that the nervous system monitors body-wide energy through dedicated interoceptive pathways fed by cellular energy sensors:

$$\text{Cellular Energy State} \xrightarrow{\text{AMPK / mTORC1}} \text{Interoceptive Body-Brain Signaling} \xrightarrow{\text{Insular Cortex}} \text{Subjective Vitality}$$

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1. AMPK (The Depletion Detector)

- When ATP is consumed, cellular AMP and ADP rise. - AMP binds regulatory sites on AMP-activated protein kinase (AMPK), and upstream kinase LKB1 phosphorylates the catalytic subunit at Thr172. - Activated AMPK halts energy-consuming programs and fires biological alarms. - High AMPK / Low ATP Ratio $\rightarrow$ The Conscious Experience of "I Have No Energy."

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2. mTORC1 (The Anabolic Sufficiency Signal)

- When amino acids, growth factors, and ATP are abundant, mTORC1 (mechanistic target of rapamycin complex 1) activates protein and lipid synthesis. - High mTORC1 / High ATP Ratio $\rightarrow$ The Conscious Experience of "I Have Energy."

By investigating interoceptive neurobiology (referencing Kleckner et al. 2021 and Filippi et al. 2022), The Human Energy Center is establishing objective biological correlates for chronic fatigue, opening pathways to measure and correct bioenergetic deficits.