Unexplained weight gain can only result from excess calorie intake and/or reduced calorie expenditure. That's what the Caloric Balance Hypothesis -- the conventional theory about why people get fat -- very clearly tells us.
The energy balance equation, from which the Caloric Balance Hypothesis derives, tells us that the only relevant part of this equation is the right side:
Energy Stored in the Body = Calories In - Calories Out
So any and all unexplained weight gain or loss that results from drug therapies, genetics, diseases, brain injuries, natural body development, hormonal or metabolic shifts, or other biochemical activity must somehow result from influence on "Calories In" and/or "Calories Out," and these changes in caloric balance in turn must regulate how much fat we put into our fat tissue.
For instance, if someone gains weight on antidepressants, it must mean that the medications increased appetite (causing the person to take in "excess" calories) or impaired metabolism (causing the person to be more sedentary and thus to burn off "fewer" calories).
The mainstream hypothesis allows for no other explanation for unexplained weight gain. The energy balance equation above, as you can see, is very simple. It says nothing about hormones. It says nothing about homeostasis in the body. It says nothing about insulin. It says nothing about the constitution of the adipose tissue. It says nothing about triglycerides or fatty acids. All it says is that consuming more calories than one needs will cause weight gain.
Similarly, unexplained weight loss on medications, etc, likewise can only result from a manipulation of energy balance. When cancer patients, for instance, suddenly start dropping pounds, it must be because they're not eating as much as they used to or because their metabolisms have somehow become overactive. That's the only explanation allowed by the Caloric Balance Hypothesis.