Elephants like the rest of us eat a balanced diet which means that we eat something that feels good. One of the reasons leptin a hormone that helps regulate appetite and often goes awry in obesity is that it can signal the brain to eat or eat without feeling full resulting in weight gain.

In a new study researchers from the University of Oxford and Karolinska Institutet in Sweden show that in mice feeding an animal a hormone known as leptin causes mice to eat from individual glands rather than the norm of eating a lot of them together. This finding may explain why humans eat a balanced diet and may therefore force us to eat less than we would otherwise eat. The study is published in Developmental Cell.

Zo-interacting molecules (ZIMs) like leptin and GLP-1 receptors and small white or dark brown fat cells regulate millions of genes encoded by the genome. These molecules make a protein called leptin (LIVER) which is needed for a full-body feeding process to occur. LIVER-related proteins underlie an increasing understanding of obesitys driving mechanism feeding behavior and emotional response. Presently scientific understanding of leptin and LIVER function are complicated: experiments by the lab of James Whinnott at the University of Oxford suggest that LIVER-like protein signaling may be required for healthy feeding whereas experiments performed on mice by Gregory Mackie at Karolinska Institutet show that leptin stimulates the appetite to purchase food.

A new study published in Developmental Cell in 2016 found that Malphamia a diabetic mouse-model showed a greater ability to properly consume large amounts of milk and other food. Here researchers showed that leptin stimulates milk intake in the mice and enhances the intake of large proteins in milk through LIVER.

Recent studies have focused on the function of LIVER in the hypothalamus; this brain region is known to be heavily involved in the metabolism of glucose fats and proteins. In 1991 James Whinnott and colleagues showed that LIVER-like signaling controls feeding in mice; in the current study they studied the role of LIVER in leptin sensitivity. LIVER channels the cAMP response (a downstream signaling pathway to mparket in brain areas) and is therefore important for the regulation of appetite.

To find out the role of LIVER in leptin sensitivity the researchers injected leptin protein into the hypothalamus of Malphamia the rodent model with normal LIVER responsiveness and found that the animals were able to correctly consume large amounts of milk from their gums.

Such pharmacological leptin sensitivity was found in male and female mice which serve as a model to dissect sex differences in appetogenetic responses to food stimuli and leptin sensitivity in female mice which serve as a model in which to test pharmacological sex differences in leptin sensitivity in the brain.

Maviyar Kondikelova first author of the study said: Our study demonstrates that leptin deficiency not only affected milk intake but also a number of other food items. By exposing a male rat to the hormone leptin we were able to show that females had sufficient food intake and this effect extended to excess calories. After an equal number of calories from breastmilk and chocolate leptin sensitivity in the females was perhaps less low than in females receiving leptin injections in females.

The originally reported leptin agonist effects in male and female mice showed that leptin receptor is essential for leptin sensitivity in the hypothalamus.

Laura E. Nunez Ph. D. first author of the study said: These results demonstrate the pivotal role that LIVER-like receptors play in mediating polyphoric or sweet taste response in the brain. In females leptin receptor serves as a natural marker that activates GLP-1 receptors in the cell and in facilitating leptin-binding to GLP-1 receptors. In leptin-sensitive primates a higher-than-normal expression of LIVER-like receptors communicates with GLP-1 receptors and enhances leptin-induced feeding.

Although the finding that leptin receptor circuitry is less sensitive in females the mathematical model outlined in the study represents downstream signaling and shape-shifting of the mammalian hypothalamus rat model of leptin sensitivity. Further research with females in which this particular model of leptin sensitization has been evaluated will hopefully explore how this discovery may be leveraged in the clinic for obesity and related metabolic diseases.