Leptin & Insulin in hunger and satiety

Leptin & Insulin in hunger and satiety

The hormonal factors involved in weight loss place both physiological and psychological action on the human body to regulate body weight.   Specifically, the two hormones leptin and insulin are crucial modulators of our physiology and our psychology that sometimes make fat loss more challenging to maintain. The relationship between leptin and insulin is a fine balance between keeping your blood sugar levels from getting too high or too low(insulin) and satiety(leptin). I like to think of insulin acting on the physiology and leptin acting on the psychology by way of physiology; leptin is partially regulated by insulin.  Both leptin and insulin can modulate eating behavior via the gut-brain axis.

Leptin is released by adipocytes and has a primary role in regulating our food intake and energy homeostasis by controlling our satiety. In other words leptin’s main role is regulation of energy balance.  The amount of leptin released by fat cells is congruent with the amount and/or size of the adipocytes. Under normal circumstances leptin increase with more fat accumulation, causing hunger to decrease; and falls with fat loss weight loss causing hunger to increase.  This is why in an extreme cases of obesity rapid weight loss is followed by a large regain of weight. Simply put, as you lose fat, leptin production decreases, making you hungrier than normal; then, the drive to eat supersedes all other aspects of control in the brain.  The number one cause of weight regain, is a lack of adherence to the diet; which is closely associated with a decrease in leptin.In the case of overeating, or hedonic obesity, patients have plenty of leptin, but have become leptin insensitive; meaning leptin no longer has the same hunger reducing effect. In any case, insulin is an important factor in the stimulation of leptin secretion. Although the mechanism is not fully understood, it is believed to be mediated by glucose metabolism.

In a study by Woods SC, Porte D Jr on the role of insulin as a satiety factor in the central nervous system, it was discovered that in peripheral tissues, insulin autophosphorylates insulin receptors, leading to activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. According the research by Niswender KD1, Morrison CD, Clegg DJ, Olson R, Baskin DG, Myers MG Jr, Seeley RJ, Schwartz MW, “ Insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. Essentially insulin not only works to shuttle glucose into cells, but it also works to regulate your satiety by way of regulating leptin.

References: 

• Juliana Austin and Daniel Marks (2009) Hormonal Regulators of Appetite.
  Retreived from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777281/

• Minglun Tsai, Akihiro Asakawa, Haruka Amitani, and Akio Inui (2012) Stimulation of leptin secretion by insulin. Retreived from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602982/

• Niswender KD1, Morrison CD, Clegg DJ, Olson R, Baskin DG, Myers MG Jr, Seeley RJ, Schwartz MW. (2003)  Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/12540590

• Rexford S. Ahima, MD, PhD and Daniel A. Antwi, PhD (2008) Brain regulation of appetite and satiety. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2710609/