Recently, most of evidence shows that caloric restriction could induce antidepressant‐like effects in animal model of depression. Based on studies of the brain–gut axis, some signal pathways were common between the control of caloric restriction and depression. However, the specific mechanism of the antidepressant‐like effects induced by caloric restriction remains unclear. Therefore, in this article, we summarized clinical and experimental studies of caloric restriction on depression. This review may provide a new therapeutic strategy for depression.

| INTRODUC TI ONDiabetes is a metabolic disease characterized by hyperglycaemia due to the defect of insulin secretion or impaired insulin biological effect. A survey has shown that about 30% of people with diabetes also suffer from depression and 10% have severe depression, which suggests a close relationship between the two diseases. 1,2 The mechanism of depression as a complication of diabetes is not completely clear, but studies have found that insulin deficiency or insulin resistance is the symptom that can also be observed in major depression disorder. [3][4][5] Insulin is the only hormone in the human body that reduces the blood glucose level and promotes the synthesis of glycogen, fat and protein. Several studies found that insulin had the ability to affect the nervous system. 6-8 Insulin receptors were distributed in other parts of the brain, except for the parts related to food intake and energy. 9-11 Experiments have gradually revealed other functions of insulin in the brain, for instance promoting memory, protecting neurons, regulating synaptic plasticity and maintaining HPA axis homeostasis. [12][13][14] These effects of insulin may provide a background for its relationship with depression. 15,16 In this case, although there is no direct evidence supporting the link between insulin and treatment for depression, more and more researches support this hypothesis. Here, we review the relationship between insulin signalling and neurophysiological homeostasis, neurotrophic metabolism, cellular pathways and some survey statistics.The exploration of these links and the validation of more relevant mechanisms will develop a new impact on the way of the diagnosis and treatment of depression. | IN SULIN AND DEPRE SS I ONAs early as 1980s, many evidences proved that insulin influenced depression and functional insulin receptors were widely present in the brain. [17][18][19] Data from clinical and epidemiological studies demonstrate a two-way link between emotion and metabolic dysfunction. In young depression patients, insulin sensitivity is significantly decreased. 20,21 Compared with "low insulin" (1.5 mU/kg × min), "high insulin" (15 mU/kg × min) induces a more pronounced of the ability to remember word lists in human being. 22 Intranasal delivery of insulin in awake mice can transmit regulatory and metabolic AbstractThe regulation of insulin on depression and depression-like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic-pituitary-adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.

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.