Role of leptin in the regulation of food intake in fasted mice

Abstract

Leptin is well acknowledged as an anorexigenic hormone that plays an important role in feeding control. Hypothalamic GABA system plays a significant role in leptin regulation on feeding and metabolism control. However, the pharmacological relationship of leptin and GABA receptor is still obscure. Therefore, we investigated the effect of leptin or combined with baclofen on the food intake in fasted mice. We detected the changes in hypothalamic c-Fos expression, hypothalamic TH, POMC and GAD67 expression, plasma insulin, POMC and GABA levels to demonstrate the mechanisms.We found that leptin inhibit fasting-induced increased food intake and activated hypothalamic neurons. The inhibitory effect on food intake induced by leptin in fasted mice can be reversed by pretreatment with baclofen. Baclofen reversed leptin's inhibition on c-Fos expression of PAMM in fasted mice. Therefore, these results indicate that leptin might inhibit fasting-triggered activation of PVN neurons via presynaptic GABA synaptic functions which might be partially blocked by pharmacological activating GABA-B. Our findings identify the role of leptin in the regulation of food intake. K E Y W O R D S baclofen, feeding behaviour, GABA-B, hypothalamus, leptin | 4525 GE Et al.

Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications

“…Leptin is produced mainly in mature cells of the WAT. Biosynthesis and secretion of leptin depends on the WAT mass and reflects the status of energy stores [74][75][76]. The main factors that affect the blood levels of leptin include fat tissue mass and adipocyte size.…”

“…These measures show a positive correlation with leptin biosynthesis in fat tissue and its level in circulating blood [18,28]. Leptin is currently considered as a satiety hormone [76]. Leptin, released into circulating blood, is transported to the brain and bound to its receptors in the hypothalamus, where it causes repression of genes encoding neuropeptide Y (NPY) and induction of genes encoding proomiomelanocortin (POMC) and corticoliberin (CRH) [75,76].…”

“…Leptin is currently considered as a satiety hormone [76]. Leptin, released into circulating blood, is transported to the brain and bound to its receptors in the hypothalamus, where it causes repression of genes encoding neuropeptide Y (NPY) and induction of genes encoding proomiomelanocortin (POMC) and corticoliberin (CRH) [75,76]. This results in decreased appetite and reduced food intake with subsequent body fat reduction and increased energy expenditure, which finally leads to body mass decrease [76].…”

“…Leptin, released into circulating blood, is transported to the brain and bound to its receptors in the hypothalamus, where it causes repression of genes encoding neuropeptide Y (NPY) and induction of genes encoding proomiomelanocortin (POMC) and corticoliberin (CRH) [75,76]. This results in decreased appetite and reduced food intake with subsequent body fat reduction and increased energy expenditure, which finally leads to body mass decrease [76]. According to some authors, in the course of evolution, leptin appeared as a factor protecting against hunger or obesity at times of availability of excess food.…”

High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring

“…In contrast, GABA, via actions on the multi-subunit GABA receptors, is associated with stimulatory effects on food intake [ 58 ]. While up-regulation of GABA A receptor subunits may seem paradoxical in the 5X-FA offspring, the physiological functions of the receptor is dependent on its unique subunit composition [ 59 ] and their neuronal distribution [ 60 ]. While the 4α- and delta- subunits are co-localized throughout the brain, their specific roles in modulating food intake are not well described.…”