The compartment routing map
The map places all 9 restoration targets on cited tissue compartments. Three named routes span the spectrum: a BAT-targeted route (the cleanest precision, UCP1 single-compartment), a central appetite-axis route (precision anatomy but a blood-brain-barrier [O] obstacle), and a hepatic glucose-disposal route (the honest distributed case -- a body-wide receptor, so a dominant-compartment route, not a single-compartment block).
The concrete table behind §R. Each row carries the target, its lever, the routing tier, the primary compartment, the parameter-free specificity (1 / compartment count), the carried γ-context (never folded in), and any [O] deliverability obstacle. The three named routes are the worked examples. Hypotheses only, firewall-bound.
The routing map
| target | lever | tier | primary compartment | specificity (n) | γ-context | cited compartment / deliverability |
|---|---|---|---|---|---|---|
| MC4R | S2 | PRECISION | hypothalamus (CNS) | 1.0000 (1) | 1.2720 | cited: MC4R energy-balance signalling is hypothalamic (paraventricular nucleus) — [O] deliverability: central access is limited by the blood-brain barrier (cited) |
| UCP1 | S2 | PRECISION | brown adipose (BAT) | 1.0000 (1) | 1.4054 | cited: UCP1 expression is essentially restricted to brown (and beige) adipocytes — [O] deliverability: the BAT depot mass is small and variable (recruitable), so reaching it is an open access problem (cited) |
| ADRB3 | S2 | REGIONAL | brown adipose (BAT) | 0.5000 (2) | 1.4462 | cited: beta3-adrenergic receptors predominate on adipocytes (brown + white / beige) |
| GHRL | S2 | REGIONAL | gut | 0.5000 (2) | 1.3550 | cited: ghrelin is produced in the stomach (gut source) and acts on hypothalamic neurons -- a gut->brain axis |
| LEPR | S1 | REGIONAL | hypothalamus (CNS) | 0.5000 (2) | 1.4554 | cited: lipostat-relevant leptin sensing is dominated by hypothalamic neurons; peripheral LEPR also present — [O] deliverability: the dominant (central) sensing site is behind the blood-brain barrier (cited) |
| PDK4 | S3 | REGIONAL | liver | 0.5000 (2) | 1.4112 | cited: the PDK4 fuel-switch operates in oxidative tissues, dominantly liver and skeletal muscle |
| PPARG | S1 | REGIONAL | white adipose | 0.5000 (2) | 1.3902 | cited: PPAR-gamma is the master adipocyte regulator, dominant in adipose tissue (white, with brown / beige) |
| INSR | S1 | SYSTEMIC | liver | 0.2500 (4) | 1.4956 | cited: the insulin receptor is ubiquitously expressed; the metabolically dominant disposal / sensing compartments are liver, skeletal muscle, adipose, and brain — [O] routability is limited: a body-wide receptor cannot be confined to one compartment; liver + skeletal muscle are the dominant disposal sub-compartments (a dominant-compartment route, not a single-compartment precision) |
| TNF | S3 | SYSTEMIC | systemic (immune) | 0.1429 (7) | — | cited: chronic low-grade inflammation is a distributed immune / stromal program with no single tissue locus — [O] routability is limited: a distributed program has no single compartment to route to (systemic by nature) |
Specificity = 1 / (cited compartment count); higher is more precisely routable. The γ-context column is the promoter switch-threshold read carried ALONGSIDE -- it never enters the specificity or the tier (proven in §R).
Three named routes
Grouped by their primary compartment, the three routes span the full honesty spectrum from a clean regional block to an inherently body-wide target:
- BAT-targeted → brown adipose (BAT): restoration aimed at the brown-fat thermogenic-disposal depot (raise disposal, S2 side) (UCP1, ADRB3 — the cleanest precision route: UCP1 acts in a single cited compartment)
- central appetite-axis → hypothalamus (CNS): restoration aimed at the hypothalamic appetite / thermostat setpoint (cut intake forcing / re-sensitise leptin) (MC4R, LEPR — anatomically routable (MC4R single-compartment) but central access is an [O] deliverability obstacle)
- hepatic glucose-disposal → liver: restoration aimed at hepatic / oxidative glucose disposal (re-sensitise insulin signalling, remove the PDK4 program) (INSR, PDK4 — the honest distributed case: INSR is body-wide, so this is a dominant-compartment route (liver + muscle), not a single-compartment precision)
Falsifiers
PR1 — If restricting a lever's action to its single cited compartment (e.g. UCP1->BAT alone) fails to move the systemic setpoint while only body-wide action does, the PRECISION (single-compartment) premise for that node is wrong -- the loop effect is not compartment-localised.
PR2 — If a node classified SYSTEMIC (distributed) turns out, in an independent compartment-restriction assay, to have its restoration effect dominated by ONE compartment, the distributed classification (and the 'cannot be locally routed' claim) is wrong.
PR3 — If a primary compartment graded routable-but-undeliverable [O] (e.g. a CNS target behind the blood-brain barrier) is in fact reached by a standard systemic route with no barrier penalty, the [O] deliverability obstacle for that node is wrong.
FRAMEWORK — If the routing specificity ordering (the cited compartment count) is uncorrelated with an independent tissue-expression-breadth readout for these nodes, the cited-anatomy basis of the routing is weakened (the classification would not hold).
Firewall
the compartment of action and the tier are [F] cited anatomy; the specificity reads the compartment count only and γ is firewalled out of it; routability [F] is distinct from deliverability [O]. These are falsifiable HYPOTHESES about where a lever acts, not a delivery prescription -- no route, device, injection, dose, efficacy, or safety claim.