(Sizzling sound effect) Doesn’t that sound just make you feel so hungry? But what’s responsible for making you feel hungry, or rather what’s responsible for making you feel un-full? The hormone Leptin.           

Leptin is a 146 amino acid-long protein that is encoded by the obesity(ob) gene. Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin is produced by adipose tissue—also known as body fat or just fat—which functions as the major storage site for fat in the form of triglycerides. Leptin reduces food intake by upregulating anorexigenic—or appetite reducing— neuropeptides, such as alpha-melanocyte-stimulating hormone, and down regulating orexigenic—or appetite-stimulating—factors, primarily Neuropeptide-Y.

Leptin crosses the blood-brain barrier to access Leptin-receptors in the hypothalamic nuclei. As opposed to water-soluble hormones, Leptin is lipid-soluble, which means that they can diffuse into the cell and bind with their leptin-receptors LEPR, which can be found in hypothalamic nuclei. When leptin binds with LEPR, it forms a complex which enables the kinase molecule JAK-2 to phosphorylate. Phosphorylated JAK-2 then phosphorylates Tyrosine-705, activating the transcription factor STAT3, which in turn alters the gene expression of specific targeted DNA sequences—particularly in neuropeptides and neurotransmitters located in the hypothalamic nuclei, which regulate food intake.

 Among these various neuropeptides is Neuropeptide-Y, or NPY. This chemical has been shown to intensely stimulate food intake. Leptin inhibits the activity of NPY neurons, while increasing the activity of alpha-melanocyte-stimulating hormones, signaling the brain that the body has had enough to eat, producing a feeling of satiety or “fullness.”

Leptin follows the simple neurohormone pathway—a change in the amount of fat is sensed by LEPR, then the hypothalamus evaluates the change, and sends signals to adipose tissue to either increase or decrease leptin production, which affects NPY and alpha-melanocyte-stimulating hormones. Leptin also follows the pattern of a negative feedback loop. It is the signal which maintains the homeostatic control of adipose tissue mass which, mentioned earlier, produces leptin. Leptin is secreted by adipose tissue in proportion to its mass, so when fat mass falls, leptin production ceases, increasing NPY activity, and therefore stimulating appetite and suppressing energy expenditure until fat mass is restored. In short, when fat mass is lost, circulating leptin levels decrease, increasing your appetite and decreasing your satiety factor, and vice versa.

Mutations in leptin receptors can lead to a constant desire for food, resulting to overfeeding and therefore obesity. Laboratory mice with a point mutation on the human obesity gene prevented the manufacture of functional leptin, leading them to become morbidly obese because leptin never signaled the mouse to stop eating. Another mutation affects the LEPR in mice, so even if leptin is produced, the brain never receives its signal. In humans, however, only a very small group of people possess the homozygous mutation for the leptin gene, so you could, theoretically, say you got your body from your momma. (will.a.Am’s “I Got It From My Mama” plays in the background).

Brief Summary: Leptin

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