Is weight loss as simple as calorie in calorie out?

Introduction
In healthy people reducing energy in and increasing energy out works exactly as predicted: the energy deficit is provided by body stores. In healthy people, homeostasis ensures that we get fat when food is abundant and lean out when food is scarce. For the obese, however, people who have been overweight for many years, homeostatic mechanisms can become broken. This is when insulin resistance leads to metabolic syndrome. The same can happen with leptin, the hypothalamus can stop sensing changes in leptin. And the same can happen for any of the other hormones and signalling mechanisms.

In a sense, the body can be impaired in its ability to self-regulate. The level of impairment varies of course, and of course some people are naturally better at it than others.

Arguments for
In this study:

http://ajcn.nutrition.org/content/88/4/906.long

It was observed that in the bodies of long term calorie reduced dieters the level of their thermal energy expenditure reduced to match the reduced calorie intake. They did not lose weight.

This is in fact the anecdotal experience of many people on a calorie reduced diet: they feel lousy, have less energy, and don't lose weight. Weight loss is a big industry precisely because it is not easy for many people who attempt it.

Cico is not the whole story, that obesity is an illness of hormonal imbalance rather than energy imbalance, and that returning homeostatic functioning (for him primarily through IF although I have a belief that there are other mechanisms).

https://intensivedietarymanagement.com/how-do-we-gain-weight-calories-part-1/[1]