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Central Nervous System Mechanisms Linking the Consumption of Palatable High-Fat Diets to the Defense of Greater Adiposity

Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
Cell metabolism (Impact Factor: 16.75). 02/2012; 15(2):137-49. DOI: 10.1016/j.cmet.2011.12.013
Source: PubMed

ABSTRACT The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention.

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    • "Please cite this article in press as: la Fleur SE, Serlie MJ, The interaction between nutrition and the brain and its consequences for body weight gain and metabolism; studies in rodents and men, Best Practice & Research Clinical Endocrinology & Metabolism (2014), http://dx.doi.org/10.1016/j.beem.2014.06.001 result in obesity with increases in both insulin and leptin levels, which in turn can inhibit reward via their receptors on dopaminergic neurons in the VTA [33e36]. However, in obesity, central leptin and insulin resistance occur [3] [4] and thus the peripheral hormonal signals might not counteract the effects of sugar and fat on the brains reward circuitry thus contributing to disrupted feeding behavior. In summary, regular consumption of high caloric food directly affects the brain circuitries involved in reward and homeostatic control of food intake, thereby increasing the risk for a food addiction like phenotype (Fig. 1). "
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    ABSTRACT: Aberrant feeding behavior can lead to obesity and obesity-related medical consequences, such as insulin resistance and diabetes. Although alterations in glucose metabolism (i.e. insulin resistance), in the presence of excessive fat tissue are often explained by the consequences of dysfunctional adipose tissue, evidence is emerging that also altered brain functions might be an important determinant of insulin resistance. In this review, we provide an overview of how feeding behavior and obesity interact with brain circuitry and how these interactions affect glucose metabolism. Because brain circuitries involved in food intake have been shown to partly control glucose metabolism as well, targeting these circuitries in obese subjects might not only affect food intake and body weight but also glucose metabolism.
    Best Practice & Research: Clinical Endocrinology & Metabolism 10/2014; DOI:10.1016/j.beem.2014.06.001
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    • "Thus, understanding the biological mechanisms regulating metabolic flexibility might lead to better therapeutic strategies tackling metabolic disorders. HFD consumption plays a significant role in the development of insulin and leptin resistance in the central nervous system (CNS) [2]. In addition, recent studies have demonstrated that nutrients are not only a source of calories, but also work as intracellular signals capable of modifying the activity of specific molecular cascades [3] [4]. "
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    ABSTRACT: Metabolic flexibility allows rapid adaptation to dietary change, however little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.Figure optionsDownload full-size imageDownload as PowerPoint slide
    08/2014; 3(7). DOI:10.1016/j.molmet.2014.07.004
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    • "(Dagogo-Jack et al., 1997; Miell et al., 1996; Newcomer et al., 1998; Slieker et al., 1996; York, 1996)newline CRH and Ucn 3 (Bernier, 2006; Ohata and Shibasaki, 2011; Smagin et al., 1998)newline CART (Kask et al., 2000; Xu et al., 2010)newline Nesfatin-1 (Goebel et al., 2009; Stengel et al., 2011)newline NPW (Beck et al., 2010)newline Melanocortins (Liu et al., 2007; Yamano et al., 2004)newline central monoaminergic systems (Gibson, 2006)newline autonomous nervous system (Seematter et al., 2000) Stress induces hyperphagia due to reduction of:newline sensor specific satiety (Ahn and Phillips, 2012; Ortolani et al., 2011)newline stressor aversiveness (Piazza and Le Moal, 1997)newline CRH signaling? (Foster et al., 2009; la Fleur et al., 2005; Pecoraro et al., 2004)newline due to activation of central reward pathways (Piazza and Le Moal, 1997),newline due to alterations in gut microbiota (Tehrani et al., 2012)newline Glucocorticoids induce hyperphagia (Dallman, 1993; Drapeau et al., 2003; Epel et al., 2000; Tataranni et al., 1996)newline due to increased signaling of:newline NPY (Gyengesi et al., 2010; Krysiak et al., 1999; McKibbin et al., 1992; White, 1993; Wilding et al., 1993),newline AgRP (Coll et al., 2005; Savontaus et al., 2002),newline Nociceptin (Green and Devine, 2009; Nativio et al., 2011; Olszewski and Levine, 2004); AgRP, agouti related peptide; NPY, neuropeptide Y; CRH, corticotrophin-releasing hormone; Ucn+, urocortin 3; CART, cocain-amphetamine related peptide; NPW, neuropeptide W. model) suggests a similar habituation to the SSS effect in rodents (Auvinen et al., 2011; Ryan et al., 2012). Moreover, rats submitted to footshock stress decreased the intake of commercial chow, but kept unaltered the intake of comfort food (Ortolani et al., 2011). "
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    ABSTRACT: The prevalence of obesity is increasing worldwide with serious consequences such as diabetes mellitus type 2 and cardiovascular diseases. Emotional stress is considered to be one of the main reasons of obesity development in humans. However, there are some contradictory results, which should be addressed. First of all stress induces anorexia, but not overeating in laboratory animals. Glucocorticoids, the effector molecules of the hypothalamo-pituitary-adrenocortical (HPA) axis stimulate and stress inhibits food intake. It is also not clear if stress is diabetogenic or an antidiabetogenic factor. The review will discusses these issues and the involvement of the whole HPA axis and its separate molecules (glucocorticoids, adrenocorticotropin, corticotropin-releasing hormone) in food intake regulation under stress.
    Brain research bulletin 04/2013; 95. DOI:10.1016/j.brainresbull.2013.04.002
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