Leptin, a 160-kDa hormone produced and secreted by the adipose tissue in direct relation to the amount of body fat, has been called the "obesity hormone" or "fat hormone" and also the "starvation hormone". When scientists discovered leptin in 1994 (Zhang, et al. 1994), excitement arose about its potential as a blockbuster weight loss treatment.
Izquierdo, et al. (2019) points out that
Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance.
You spoke of leptin receptors saying
a decrease in the leptin receptor number could produce a feeling of fullness.
There is only one leptin receptor. The leptin receptor, also known as ObR, is a single membrane-spanning receptor belonging to the class I cytokine receptor family (Wauman, et al. 2017) and it is either efficient in detecting leptin levels or it is not. A decrease in leptin, or the condition of leptin resistance as discussed by Izquierdo, et al. (2019), would increase appetite and therefore increase hunger levels. Continuous low leptin levels or leptin resistance will lead to an increase in body weight to the point of obesity.
An increase in leptin, or high leptin receptor activity, would suppress appetite due to an induced feeling of fullness. Continuous high levels will lead to starvation and weight loss.
It is a balancing act.
Under normal conditions, the balance between leptin and the leptin receptor (ObR) regulates body weight by balancing food intake and energy expenditure (Wauman, et al. 2017).
Everyone has their individual leptin level threshold.
WebMD explains this as follows, quoting Robert H. Lustig, MD, professor of pediatrics at the University of California, San Francisco:
"Leptin tells your brain that you have enough energy stored in your fat cells to engage in normal, relatively expensive metabolic processes," he says. "In other words, when leptin levels are at a certain threshold — for each person, it's probably genetically set — when your leptin level is above that threshold, your brain senses that you have energy sufficiency, which means you can burn energy at a normal rate, eat food at a normal amount, engage in exercise at a normal rate, and you can engage in expensive processes, like puberty and pregnancy".
But when people diet, they eat less and their fat cells lose some fat, which then decreases the amount of leptin produced.
"Let's say you starve, let's say you have decreased energy intake, let's say you lose weight," Lustig says. "Now your leptin level goes below your personal leptin threshold. When it does that, your brain senses starvation. That can occur at any leptin level, depending on what your leptin threshold is."
"Your brain senses that and says, ‘Hey, I don't have the energy onboard that I used to. I am now in a starvation state,'" Lustig says.
Then several processes begin within the body to drive leptin levels back up. One includes stimulation of the vagus nerve, which runs between the brain and the abdomen.
"The vagus nerve is your energy storage nerve," Lustig says. "Now the vagus nerve is turned on, so you get hungrier. Every single thing the vagus nerve does…[is] designed to make you take up extra energy and store it in your fat. Why? To generate more leptin so that your leptin can re-establish its personal leptin threshold... It causes you to eat and it causes you to get your leptin back to where it belongs."
References
Izquierdo, A. G., Crujeiras, A. B., Casanueva, F. F., & Carreira, M. C. (2019). Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?. Nutrients, 11(11), 2704. https://doi.org/10.3390/nu11112704
Wauman, J., Zabeau, L., & Tavernier, J. (2017). The leptin receptor complex: heavier than expected?. Frontiers in endocrinology, 8, 30. https://doi.org/10.3389/fendo.2017.00030
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372(6505), 425–432. https://doi.org/10.1038/372425a0
