Abstract:HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS.
“…There were no changes in the expression of transcript encoding for NPY and POMC (data not shown). The immunoneutralization of LIF in the hypothalamus resulted in reduced STAT3 Tyr705 phosphorylation in the hypothalamus but not in the hippocampus [ 14 ] (Additional file 1 : Figure S2), suggesting that the method was appropriate for a site-specific action of the antibody. Fig.…”
BackgroundThe consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation.MethodsWe used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet.ResultsUsing a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance.ConclusionHypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0956-9) contains supplementary material, which is available to authorized users.
“…There were no changes in the expression of transcript encoding for NPY and POMC (data not shown). The immunoneutralization of LIF in the hypothalamus resulted in reduced STAT3 Tyr705 phosphorylation in the hypothalamus but not in the hippocampus [ 14 ] (Additional file 1 : Figure S2), suggesting that the method was appropriate for a site-specific action of the antibody. Fig.…”
BackgroundThe consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation.MethodsWe used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet.ResultsUsing a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance.ConclusionHypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0956-9) contains supplementary material, which is available to authorized users.
“…High fat diet (HFD)-induced obesity in rodents is associated with hypothalamic inflammation, a pathological state that is a key characteristic of the disease. In rodents, LIF is downregulated in both the nucleus tractus solitarus of the brainstem and hypothalamus in response to HFD [83,84]. Importantly, LIF can act upon LIF receptors on POMC neurons in an anorexigenic manner by stimulating the release of alpha MSH [85].…”
Section: Leukaemia Inhibitory Factormentioning
confidence: 99%
“…Importantly, LIF can act upon LIF receptors on POMC neurons in an anorexigenic manner by stimulating the release of alpha MSH [85]. Both central and peripheral administration of LIF in rodents reduces body weight [84,86,87].…”
Efficacy of obesity treatments varies between individuals, highlighting the presence of responders and non-responders. Whilst exercise alone or exercise combined with diet leads to underwhelming weight loss for most, there exist super responders losing significant weight. Furthermore, in response to weight loss, the majority but not all patients tend to regain weight. Within the biopsychosocial model, biology as a determinant of response has been underappreciated. The understanding of the role that organs beyond adipose tissue and the gastrointestinal tract play in appetite control and body weight regulation has developed in recent years. The aim of this review is to highlight potential myokines that may be important in appetite physiology and overall energy balance. A number of attractive targets are described that warrant further investigation. A deeper understanding of how these myokines may drive feeding behaviours has the potential to improve measures to prevent and treat obesity through a precision medicine approach.
“…It was observed that hypothalamic inhibition of this factor in obesity-resistant mice switched them into the obesity-prone phenotype, which indicates that this adipokine is an obesity-protectant [ 221 ]. On the other hand, a high-fat diet decreased the LIF gene transcription in the brain stems of rats which may contribute to permissive overconsumption and the development of diet-induced obesity [ 93 ]. Moreover, it plays a role in the pathology of various diseases including cancers [ 222 ].…”
Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. They suspect that a potential cause of its development is connected to the biology of adipokines, active molecules secreted by adipose tissue. Under physiological conditions, adipokines control many processes, including lipid and glucose homeostasis, insulin sensitivity, angiogenesis, and inflammations. However, when there is an increased amount of fat in the body, their secretion is dysregulated. This article reviews the current knowledge of the effect of adipokines on melanoma growth. This work focuses on the molecular pathways by which adipose tissue secreted molecules modify the angiogenesis, migration, invasion, proliferation, and death of melanoma cells. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Further studies may contribute to the innovations of therapies and the use of adipokines as predictive and/or prognostic biomarkers.
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