Leptin, Ghrelin, Adiponectin, and Resistin: Fat and Hungry

So I recently realized that I don't know nearly enough about mammalian metabolism, or my own, really. Therefore, naturally, I turned to my best friends for answers: PubMed and Google Scholar. I learned some stuff. And now I'm going to learn you some stuff about the metabolic hormones.

We all know about insulin, even if we have no idea what it does. Basically, you eat stuff. Stuff has sugar. Stuff + stuff sugar gets absorbed across intestinal epithelium into your bloodstream. Serum levels of glucose rise and the beta cells in the islets in the pancreas are all like "Yo, I got this!", so they release insulin, which goes out into the bloodstream and tells the other cells, specifically those in hepatic and adipose tissues (and skeletal muscle for the picky), to get up and upregulate the surface proteins that take glucose out of the blood and do stuff with it. Like make glycogen or do some fatty acid reduction of glucose into triglycerides and stuff. Net result: insulin reduces bloodstream levels of glucose when they're high.

Not as many people know about glucagon. Glucagon is insulin's arch-nemesis. When bloodstream glucose is lower than it should be (when you haven't recently eaten), glucagon gets released and tells those same tissues that stored it to start releasing glucose back into the bloodstream so that tissues without much glucose/glycogen storage capacity (like your brain) can continue to eat and survive and stuff. Net result: glucagon increases bloodstream levels of glucose when they're low.

This is all well and good, but how do the stomach, brain, and fat communicate?

Enter Leptin, Adiponectin, Ghrelin, and Resistin.

Leptin makes you sated,
Ghrelin makes you hunger
Resistin's role is still debated
Adiponectin's from your blubber

Leptin is secreted by adipose tissue, which is just a polite way of saying that it's made by fat. The more fat present: the more baseline leptin gets secreted; although as the levels of leptin increase some fancy stuff starts to happen with its receptors, of which there are several isoforms. Leptin acts and peaks in concert with insulin to stimulate uptake of glucose and fat storage, but it also acts upon the hypothalamus to make you feel full after you've started eating. This is interesting because it suggests that feeling full has a lot more to do with blood glucose level's effect on the circulating leptin than actual stomach volume. Maybe this is why Snickers bars can sometimes be sorta filling. It is thought that in normal feeding patterns, leptin functions as a sensor of total body fat ratio and possibly as a link to the reproductive system as a switch on whether sufficient energy reserves are present for normal reproductive function.

Ghrelin is unique in that it is a hormone that comes from your tummy, directly from the fundus of the stomach. It binds GHS-R in the arcuate nucleus of the hypothalamus and has been shown to cause a release of growth hormone. Ghrelin makes you feel hungry and is associated with increased stomach motility and increased secretion of gastric juices (grumbling tummy).

Adiponectin is secreted by adipose tissue as well. Adiponectin increases insulin sensitivity in adipose tissue and also improves the glucose response. As BMI increases, adiponectin secretion decreases, thus acting kind of as a sensor for total body fat (although leptin kind of does that, too) but at the same time making fat less sensitive to insulin and thus more prone to diabetes.

Resistin is poorly understood in humans as it has been primarily characterized in rats. It is, however, associated with insulin resistance at increased concentrations and is secreted more at higher BMIs.

And this is just the tip of the iceberg for this subject. There're also orexins, neuropeptide Y, the effects of IGFs, PPARs, glucocorticoids, beta-adrenergic stuff and more. I know this post was a bit shallow on details and as such will probably offend real metabolic scientists, but it was a 15-page or so review, so I had to be be choosy.

Abstract:
BACKGROUND: Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism. APPROACH: This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry. CONTENT: Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site. SUMMARY: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.

I really am enamored of/amused by the technical writing-mandated tautology of "SUMMARY: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized."
Meier, U. (2004). Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin Clinical Chemistry, 50 (9), 1511-1525 DOI: 10.1373/clinchem.2004.032482