How the body regulates weight

Human biology evolved under scarcity, infection, physical danger and instability. The systems that regulate hunger, fat storage and energy expenditure were shaped for survival in that world, not for constant and effortless abundance. This distinction matters: a system doing what it evolved to do presents a different problem from a system that has broken down.

• Mismatch Evolved systems, and an environment that changed faster than they could.
• Microbiome What industrialized guts lost, and the much larger claim that does not follow from it.

Under normal conditions, body weight is held within a range by continuous communication among the brain, fat tissue, hormones and the gut. The system runs without your attention. Understanding what goes wrong in obesity begins with understanding how this regulation works when it is intact.

• Leptin The stored-energy signal, and what happens when the brain receives less of it.
• Ghrelin The hunger hormone, and what stomach procedures do to it.
• The gut-brain connection The pathways that carry these signals between the gut and the brain.

The same systems that once protected survival can become chronically overstimulated in an environment of abundance, inactivity and disrupted sleep. The weight the body defends drifts upward, and the signaling that should resist the drift is the signaling that has been blunted.

• Upward drift Start here Why the weight the body defends rises over time.
• Metabolic dysregulation What goes wrong in the body while the defended range is rising.
• Rewilding Six conditions, with the size of each effect stated plainly.

Modern treatments work because they alter that signaling, whether mechanically, hormonally or anatomically. What follows describes what each option does, what the evidence shows, and what it costs. Start with the overview →

• How GLP-1s work What they do, and what happens when you stop taking them.
• How ESG works Capacity and timing, rather than hunger hormones.
• Medication vs. procedure The trade-offs, with neither option declared the winner.
• How to think about regain A predictable biological response, not a failure of discipline.
• What comes after the drugs The duodenum, the ghrelin-producing lining, and matching treatment to the person, all of it early-stage and presented as such.
• How reversible are the options One word that is used to mean four different things.