Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012

The hypothalamus is a crucial subcortical brain region that serves as a key control centre for regulating adipocyte mass.

“The hypothalamus is a crucial subcortical brain region that serves as a key control centre for regulating adipocyte mass.93”

The prefrontal cortex is crucial for cognitive-based inhibitory control of food intake.

“This region is crucial for cognitive-based inhibitory control of food intake.93”

Dysregulation in neural circuits can lead to an imbalance between energy intake and expenditure, promoting uncontrolled fat accumulation, weight gain, and the development of obesity.

“Dysregulation in these neural circuits can lead to an imbalance between energy intake and expenditure, promoting uncontrolled fat accumulation, weight gain, and the development of obesity.93”

Disruption of genes in the leptin-melanocortin pathway alters eating behaviour by increasing hunger, decreasing satiety, activating food reward cues, and increasing the preference for dietary fat.

“In particular, disruption of genes in the leptin-melanocortin pathway alters eating behaviour by increasing hunger, decreasing satiety, activating food reward cues, and increasing the preference for dietary fat.”

NTS neurons express receptors for multiple satiety peptides such as leptin, melanocortin, and GLP-1, and are key contributors to satiety control.

“NTS neurons express receptors for multiple satiety peptides such as leptin, melanocortin, and GLP-1, and are key contributors to satiety control.93”

If a patient has obesity, this can change the hippocampus, affecting food-related memory and cognitive processes, potentially influencing eating behaviours.

“If a patient has obesity, this can change the hippocampus, affecting food-related memory and cognitive processes, potentially influencing eating behaviours.93”

Genome-wide association studies have identified several hundred common variants that influence food intake, basal metabolic rate, and the energy used during a fixed amount of exercise.

“Genome-wide association studies have identified several hundred common variants that influence food intake, basal metabolic rate, and the energy used during a fixed amount of exercise.92–94”

In obesity, there can be dysregulation in the VTA's dopaminergic signalling, contributing to the reinforcement of overeating behaviours.

“In obesity, there can be dysregulation in the VTA’s dopaminergic signalling, contributing to the reinforcement of overeating behaviours.93”

Eating is both an innate (hard-wired) and learned behaviour.

“These findings show that eating is both an innate (hard-wired) and learned behaviour.93”