Peptide hormones regulating appetite: Focus on neuroimaging studies in humans

In recent years, knowledge about hormonal feedback from the gastrointestinal tract and adipose tissue has increased tremendously. Peptide hormones modulating hunger have been intensively studied, mostly in animals but increasingly also in humans. The first therapeutic agents, such as GLP-1 analogues, are in successful clinical use for T2D and may beneficially affect hunger and reduce weight. Data from in vitro studies and animals provide detailed insight into regulatory mechanisms leading to peptide secretion and receptor bindings, as well as to the distribution of receptors involved in different parts of the body. With neuroimaging techniques human brain structures have been identified that play a role in hunger, satiety and eating behaviour. These include the primary gustatory (insular) and olfactory (pyriform) cortex and regions with a highly permeable blood-brain barrier (hypothalamus, brain stem), which facilitates humoral input via gut peptides and leptin. In addition, cerebral networks involved in higher cognitive functions, especially those relevant to reward, pleasure and also addiction (ventral and dorsal striatum, amygdala, orbitofrontal cortex (OFC), prefrontal cortex (PFC)) were shown to be involved. First indications of direct influences of peptide hormones on these networks have become available from neuroimaging studies administrating synthetic PYY, ghrelin and leptin. Insulin also appears to play an important role as a central satiety hormone, and evidence indicating the possibility of central insulin resistance in obesity is available

Food-seeking behavior is triggered by skin ultraviolet exposure in males.

Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53-chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases

Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition

Metastatic melanoma is one of the most deadly and evasive types of cancer. On average, cancer patients with metastatic melanoma survive only 6–9 months after diagnosis. Epidemiological and animal studies suggest that obesity increases the metastatic ability of malignant melanoma, though the mechanism is not known. In the present studies, we assessed the ability of 3T3L1 adipocytes to modulate B16BL6 melanoma cell invasion and the Epithelial-to-Mesenchymal Transition (EMT). For this purpose, we induced the differentiation of 3T3L1 fibroblasts to adipocytes. Then, we collected the cell culture media from both fibroblasts and adipocytes and determined their effect on the invasive ability and EMT gene expression of B16BL6 melanoma cells. Results show that adipocyte media increased that ability of B16BL6 cells to invade. The higher invasive ability of B16BL6 melanoma cells was associated with increased expression of EMT genes such as Snai1, MMP9, Twist, and Vimentin. Additionally, the expression of the cell-to-cell adhesion protein E-cadherin and the metastasis suppressor gene Kiss1 were down-regulated in these B16BL6 cells. Also, adipocytes had high levels of the pro-inflammatory cytokine Interleukin 6 (IL-6). Treatment of B16BL6 cells with IL-6 elicited similar effects as the adipocyte media; IL-6 promoted the invasive ability of B16BL6 melanoma cells, increased the expression of Snai1, and decreased Kiss1 expression. IL-6 neutralization, however, did not have a visible effect on adipocyte media-induced invasion and snai1 staining. In summary, adipocytes may increase the invasive ability of B16BL6 melanoma cells by promoting EMT and decreasing the expression of genes such as E-cadherin and Kiss1