Student Theses and Dissertations


Caner Caglar

Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Friedman Laboratory


Leptin deficient ob/ob mice eat voraciously and their food intake is markedly reduced by leptin treatment. Leptin acts in part by regulating the activity of AGRP neurons and POMC neurons in the arcuate nucleus and neurons in other brain regions. In these dissertation, I will describe how we identify novel neuronal populations that are regulated by leptin directly or indirectly. In order to identify novel sites of leptin action, we used phosphotrap, to molecularly profile leptin responsive neurons in the hypothalamus and brain stem. In addition to identifying several known leptin responsive populations, we found that neurons in Dorsomedial Hypothalamus (DMH) expressing GSBS are activated in ob/ob mice and suppressed by leptin treatment. Because ob mice are hyperphagic, we hypothesized that GSBS neurons would activate food intake. However excitation of GSBS neurons decreased food intake and body weight in ob/ob mice while chemogenetic inhibition of GSBS neurons increased food intake and body weight. The DMH regulates Food Anticipatory Activity (FAA) and in a scheduled feeding protocol that elicits increased consumption, mice also ate more when GSBS neurons were inhibited and less when they were activated without altering food anticipatory activity, body temperature and oxygen consumption. GSBS neurons do not express the leptin receptor suggesting that GSBS neurons in the DMH play a key role to restrict excessive food intake when consumption is increased and that leptin suppresses their activity indirectly by reducing food intake. These findings reveal that neural pathways activated by acute increases of food intake can restrain food intake independent of metabolic state. This finding has potential implications for an understanding of binge eating and other nutritional disorders.


A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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