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LA PLACE DES LIPIDES DANS L’ALIMENTATION Central lipid detection and the regulation Abstract: The modern abundance of energy-rich foods combined with a shift to more sedentary lifestyles has led to a thermodynamic imbalance in which excessive caloricintake and reduced energy expenditure account for the prevalence of obesity. In particular, exposure to lipid-rich diet is thought to promote metabolic alteration in peripheral tissue associated with obesity-related diseases. The regulation of energy balance depends on the ability of the brain to provide an adaptive response to change in circulating factors of hunger and satiety. The hypothalamus is particularly regarded as key integrative structure but, aside from hypothalamic-mediated homeostatic control, feeding behavior is also modulated by sensory inputs, such as tastes and odors, as well as by affective or emotional states. The reinforcing and motivational aspects of food areclosely tied to the release of the neurotransmitter dopamine by the mesolimbic system, which is stimulated by calorie-dense foods as well as by most other objects of desire.
Therefore feeding behavior is regulated by homeostatic as well as non-homeostatic inputs from the hypothalamus and the mesolimbic region. Interestingly, these structures expresses several enzymes involved in the processing of triglyceride and fatty acid and the recent literature provide growing evidence that fatty acid metabolism within discrete brain regions can function as sensor of nutrient availability directly control the hedonic 4 rue Marie-Andree Lagroua Weill-Halle, and the homeostatic aspect of feeding.
Key words: Free fatty acid, triglycerides, lipoprotein lipase, mesolimbic system, reward, piece 512A,Case courrier 7126,75205 Paris Cedex 13,France restriction) invariably result in a rapid return to ‘‘set point’’ when normal this, circulating peripheral factors such as hormones (e.g., insulin, leptin, ghrelin) sedentary lifestyles has led to a thermo- and nutrients (e.g., glucose, lipids) acti- vate discrete neural circuits in the brain fact that globally, there has been both an bolic rate and/or feeding behaviour.
that are high in fat, salt and a decrease in rodent models. Therefore it is crucial to understand the mechanism that insuresthe proper equilibrium between energyintake and expenditure.
Several observations led to the identifi- To cite this article: Cansell C, Luquet S. Central lipid detection and the regulation of feeding behavior. OCL 2013; 20(2): 93-101. doi : cle. They are called ‘‘first order neurons’’ factors like insulin, ghrelin or leptin.
circulating factors of hunger and satiety Blood Barrier (BBB) is less developed.
inputs, such as tastes and odors, as well High fat feeding and in general lipid & receptors. ARC neurons project to ‘sec- other brain areas, essential for the long- like Nucleus of the Solitary Tract (NTS).
were also link to the establishment of an other objects of desire (e.g., sex, drugs) cortin system leads to obesity andhyperphagia in both human and rodent In particular, the projection of midbrain feeding and in obese state could directly brain regions is a crucial neural substrate effect; and thus this projection is often referred to as the brain ‘‘reward circuit’’.
poorly studied for long time, as they were data attest that cerebral lipids come from be pointed that structure and function of the BBB within hypothalamus – especial- cular organs (CVO) – is quite different are characterized by their small size, high nuclei involved in food intake, including that do not cross BBB in other part of the both free fatty acid and triglyceride rich particles (TG). Elevated circulating levels dence that ‘‘central lipid sensing sens- ing’’ is involved in the control of feeding areas playing a critical role in the control (FAS) or the Carnitine Palmitoyltransfer- ase 1 (CPT-1) leads to a decrease in food cally relevant satiety signal acting in the sufficiently for survival, whereas restora- tion of DA in the Nacc is not sufficient to nists of DA receptor), sufficient to render ful determinant of food intake. Ingestion ulenin – another inhibitor of FAS – alter particularly if the food is rich in sugar or the expression profiles of feeding-related comfort in depression or stressful states contributes to weight loss. In vitro and in vivo studies demonstrate that at least part processes were termed ‘‘liking’’ and ‘‘wanting’’, respectively. With regard 5’-AMP kinase activator, rapidly lowers (ACC), an established target of AMPK.
Collectively, these data suggest a role for activate intracellular signaling pathways Solitarius (NTS), the parabrachial nucle- tially. Other circulating parameters like firing rate of VTA DA neurons and i.c.v.
directly affect feeding behavior. In fact, potential role of insulin in dopaminergic greater desire for high-calorie foods.
over, i.c.v. leptin and insulin infusion or dopamine cells and their projections into regions involve in the rewarding aspect of late DA neuron activity. The role of these tions in brain circuits, other than those regulate hunger and satiety, are involved Leptin, insulin and ghrelin receptors are while increasing level of ghrelin; each of (i.c.v.) insulin administration increased and eating behavior, thus it is premature in response to an intravenous infusion of tion (20 days) significantly increased D2 feeding behavior and leading to obesity.
typically a function of its fat and sugar particularly lipids, could act directly on tine/i.p. bromocriptine injection) partly consistent with the fact that electrically in mice that are inherent resistant to the dently of weight gain, at the early stage tion. In fact, animals consuming high fat alter mesolimbic insulin action. In fact, access to cafeteria diet decreased striatal insulin-activated signaling kinase (Akt).
activation of striatal DA target regions in suppose that nutritional lipids present in (stimulated with pictures of high-calorie striatal activation in response to palat- rewarding and hedonic value of food.
associated with behavioral defaults like a lipid levels and cognitive function is still impaired acquisition in several cognitive of food are closely tied to the release of fore relay the action of TG-rich particle, paradigms in normal body weight mice.
as well as by most other objects of desire seen in obesity such as food reward lever sory reward of fat is bypassed with i.p.
(NAc) and other limbic brain regions is a of the author at the 2012 Journee of thegroup lipid nutrition. This work was morphine) exert their effect; and thus this projection is often referred to as the brain ‘‘reward circuit’’. Strong evidence indi- ‘‘Agence Nationale de la Recherche’’ neurons of the brain reward circuit which effects of palatable food. Interestingly, underlie key aspects of the addictive state obesity prone rats still at normal weight days of access to HF diet) had levels ofTG consistently higher in response to tail both ‘‘homeostatic’’ inputs, arising Abbott NJ, Ronnback L, Hansson E. Astrocyte- endothelial interactions at the blood-brain ute to the failure of obesity-prone rats to barrier. Nat Rev Neurosci 2006; 7: 41-53.
properly regulate their intake of a high- Abizaid A, Liu ZW, Andrews ZB, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neuronswhile promoting appetite. J Clin Invest 2006; primary source of energy, it expressesseveral enzymes involved in the trans- Alsio J, Olszewski PK, Norback AH, et al.
Several observations led to the identifi- differs depending on diet-induced obesity phenotype in rats. Neuroscience 2010; 171: Arase K, Fisler JS, Shargill NS, York DA, Bray 3-OHB and insulin in a rat model of dietary circulating factors of hunger and satiety obesity. Am J Physiol 1988; 255: R974-81.
Beck B. KO’s and organisation of peptidergic Lpl, selectively in neurons translate into receptor density in the striatum. Neuroreport inputs, such as tastes and odors, as well as CH, Schotz MC. Synthesis and regulation of lipoprotein lipase in the hippocampus. J Lipid Berridge KC, Robinson TE. What is the role of neurons regulates feeding. Neuron 2006; 51: dopamine in reward: hedonic impact, reward Sherwin RS. Glucose modulates rat substantia learning, or incentive salience? Brain Res Brain nigra GABA release in vivo via ATP-sensitive Hu Z, Dai Y, Prentki M, Chohnan S, Lane MD.
potassium channels. J Clin Invest 1995; 95: A role for hypothalamic malonyl-CoA in the Bruce-Keller AJ, Keller JN, Morrison CD.
control of food intake. J Biol Chem 2005; 280: Obesity and vulnerability of the CNS. Biochim Echo JA, Lamonte N, Ackerman TF, Bodnar RJ.
Alterations in food intake elicited by GABA Jerlhag E, Egecioglu E, Dickson SL, Andersson and opioid agonists and antagonists admin- M, Svensson L, Engel JA. Ghrelin stimulates Richardson S, Convit A. Modifiers of cognitive function and brain structure in middle-aged mine-overflow via central cholinergic sys- and elderly individuals with type 2 diabetes mellitus. Brain Res 2009; 1280: 186-94.
Farr SA, Yamada KA, Butterfield DA, et al.
chronic food restriction: behavioral evidence cognitive impairment. Endocrinology 2008; receptors in addiction-like reward dysfunc- Figlewicz DP, Bennett J, Evans SB, Kaiyala K, tion and compulsive eating in obese rats.
Colantuoni C, Schwenker J, Mccarthy J, et al.
Sipols AJ, Benoit SC. Intraventricular insulin Nature neuroscience 2010; 13: 635-41.
and leptin reverse place preference condi- Kalra SP, Dube MG, Sahu A, Phelps CP, Kalra PS, Neuropeptide. Y secretion increases in brain. Neuroreport 2001; 12: 3549-52.
the paraventricular nucleus in association Figlewicz DP, Bennett JL, Naleid AM, Davis C, with increased appetite for food. Proc Natl Grimm JW. Intraventricular insulin and leptin disorders. Prog Brain Res 2000; 126: 325-41.
decrease sucrose self-administration in rats.
Leibowitz SF. Circulating triglycerides after a central melanocortin system. Nat Neurosci Figlewicz DP, Evans SB, Murphy J, Hoen M, high-fat meal: predictor of increased caloric Baskin DG. Expression of receptors for insulin and leptin in the ventral tegmental area/ and dietary obesity. Brain Res 2009; 1298: Dallman MF, Pecoraro N, Akana SF, et al.
substantia nigra (VTA/SN) of the rat. Brain Res Chronic stress and obesity: a new view of ‘‘comfort food’’. Proc Natl Acad Sci U S A Kelley AE, Bakshi VP, Haber SN, Steininger TL, Figlewicz DP, Macdonald Naleid A, Sipols AJ.
Will MJ, Zhang M. Opioid modulation of taste hedonics within the ventral striatum. Physiol Dallman MF, Pecoraro NC, La Fleur SE.
signals. Physiol Behav 2007; 91: 473-8.
Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Figlewicz DP, Szot P, Chavez M, Woods SC, Kelley AE, Baldo BA, Pratt WE. A proposed Veith RC. Intraventricular insulin increases hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and Davis JF, Tracy AL, Schurdak JD, et al.
substantia nigra. Brain Res 1994; 644: 331- food reward. J Comp Neurol 2005; 493: 72- Exposure to elevated levels of dietary fat mesolimbic dopamine turnover in the rat.
Fulton S, Pissios P, Manchon RP, et al. Leptin Kim EK, Miller I, Landree LE, et al. Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treat- Davis LM, Michaelides M, Cheskin LJ, et al.
ment. Am J Physiol Endocrinol Metab 2002; Bromocriptine administration reduces hyper- Gao S, Lane MD. Effect of the anorectic fatty phagia and adiposity and differentially affects Kotz CM, Billington CJ, Levine AS. Opioids in binding in leptin-receptor-deficient Zucker stem. Proc Natl Acad Sci U S A 2003; 100: the nucleus of the solitary tract are involved in rats and rats with diet-induced obesity.
feeding in the rat. Am J Physiol 1997; 272: Neuroendocrinology 2009; 89: 152-62.
Geiger BM, Behr GG, Frank LE, et al. Evidence for defective mesolimbic dopamine exocyto- Krugel U, Schraft T, Kittner H, Kiess Willes P.
sis in obesity-prone rats. FASEB J 2008; 22: Basal and feeding-evoked dopamine release oder-van der Elst JP, et al. Pharmacologi- in the rat nucleus accumbens is depressed mediated transmission alters the metabolic resistant C57Bl6 mice. Exp Diabetes Res 2011; Lam TK, Pocai A, Gutierrez-Juarez R, et al.
rat dietary obesity. Neuroscience 2009; 159: Hypothalamic sensing of circulating fattyacids is required for glucose homeostasis.
De Leon J, Diaz FJ, Josiassen RC, Cooper TB, blind multidosage clozapine study. J Clin Lam TK, Schwartz GJ, Rossetti L. Hypotha- lamic sensing of fatty acids. Nat Neurosci Drewnowski A, Shrager EE, Lipsky C, Stellar E, dysfunction in otherwise healthy adults.
Leddy JJ, Epstein LH, Jaroni JL, et al. Influence hedonic evaluation of liquid and solid foods.
Hommel JD, Trinko R, Sears RM, et al. Leptin of methylphenidate on eating in obese men.
Levine AS, Olszewski PK, Mullett MA, et al.
Speed N, Saunders C, Davis AR, et al.
Intra-amygdalar injection of DAMGO: effects Mangiarini L, Heidbreder C, Hedou G.
Impaired striatal Akt signaling disrupts dopa- on c-Fos levels in brain sites associated with Systemic administration of ghrelin increases mine homeostasis and increases feeding.
feeding behavior. Brain Res 2004; 1015: 9-14.
extracellular dopamine in the shell but not Malik S, Mcglone F, Bedrossian DDagher A.
the core subdivision of the nucleus accum- Stice E, Spoor S, Bohon C, Small DM. Relation Ghrelin modulates brain activity in areas that bens. Neurochem Int 2009; 54: 89-94.
control appetitive behavior. Cell Metab 2008; Rada P, Bocarsly ME, Barson JR, Hoebel BG, Mansour A, Khachaturian H, Lewis ME, Akil H, in Sprague-Dawley rats prone to overeating a Stoeckel LE, Weller RE, Cook EW 3rd, Twieg Watson SJ. Autoradiographic differentiation fat-rich diet. Physiol Behav 2010; 101: 394- of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci Rapoport SI. In vivo fatty acid incorporation in response to pictures of high-calorie foods.
into brain phosholipids in relation to plasma Migrenne S, Le Foll C, Levin BE, Magnan C.
availability, signal transduction and mem- Brain lipid sensing and nervous control of brane remodeling. J Mol Neurosci 2001; 16: JM. Beta-endorphin in brain limbic struc- tures as neurochemical correlate of psychic Ronnett GV, Kim EK, Landree LE, Tu Y. Fatty Figlewicz DP. The action of leptin in the treatment. Physiol Behav 2005; 85: 25-35.
Szczypka MS, Kwok K, Brot MD, et al.
Ronnett GV, Kleman AM, Kim EK, Landree LE, intake is dependent on Jak-2 signaling. Am men restores feeding in dopamine-deficient J Physiol Endocrinol Metab 2009; 297: E202- nervous system, and feeding. Obesity (Silver Spring) 2006; 14 (Suppl. 5): 201S-7S.
Rothemund Y, Preuschhof C, Bohner G, et al.
AS. Ghrelin induces feeding in the mesolim- Differential activation of the dorsal striatum Snyder RO, Leff SE, Palmiter RD. Viral gene by high-calorie visual food stimuli in obese delivery selectively restores feeding and tegmental area and the nucleus accumbens.
individuals. Neuroimage 2007; 37: 410-21.
Ruge T, Hodson L, Cheeseman J, et al. Fasted Obici S, Feng Z, Morgan K, Stein D, Karkanias to fed trafficking of Fatty acids in human Tu Y, Thupari JN, Kim EK, et al. C75 alters G, Rossetti L. Central administration of oleic adipose tissue reveals a novel regulatory step central and peripheral gene expression to acid inhibits glucose production and food for enhanced fat storage. J Clin Endocrinol Palmiter RD. Is dopamine a physiologically increases in the firing rate of central dopami- decreases sucrose intake of rat pups inindependent ingestion tests. Pharmacol Bio- nergic neurons. Science 1980; 210: 1269-71.
dorsal striatum is essential for motivated Schwartz MW, Porte D Jr. Diabetes, obesity, behaviors: lessons from dopamine-deficient and the brain. Science 2005; 307: 375-9.
mice. Ann N Y Acad Sci 2008; 1129: 35-46.
Schwartz MW, Woods SC, Porte D Jr, Seeley implications for obesity. Trends Cogn Sci Paradis E, Clavel S, Julien P, et al. Lipoprotein RJ, Baskin DG. Central nervous system control lipase and endothelial lipase expression in of food intake. Nature 2000; 404: 661-71.
mouse brain: regional distribution and selec- Volkow ND, Wang GJ, Telang F, et al. Inverse Sipols AJ, Bayer J, Bennett R, Figlewicz DP.
tive induction following kainic acid-induced Intraventricular insulin decreases kappa opi- lesion and focal cerebral ischemia. Neurobiol metabolic activity in healthy adults. Obesity oid-mediated sucrose intake in rats. Peptides Pardini AW, Nguyen HT, Figlewicz DP, et al.
Distribution of insulin receptor substrate-2 in Feeding-induced dopamine release in dorsal dopamine striatal D2 receptors are associated brain areas involved in energy homeostasis.
striatum correlates with meal pleasantness with prefrontal metabolism in obese subjects: ratings in healthy human volunteers. Neuro- possible contributing factors. Neuroimage Pickel VM, Sumal KK, Beckley SC, Miller RJ, Reis DJ. Immunocytochemical localization of Wang GJ, Volkow ND, Logan J, et al. Brain Sorensen A, Travers MT, Vernon RG, Price NT, enkephalin in the neostriatum of rat brain: a Barber MC. Localization of messenger RNAs light and electron microscopic study. J Comp encoding enzymes associated with malonyl- Wang H, Astarita G, Taussig MD, et al.
Pocai A, Lam TK, Gutierrez-Juarez R, et al.
Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance patic glucose production. Nature 2005; 434: and leads to obesity. Cell Metab 2011; 13: Prodi E, Obici S. Minireview: the brain as Wang H, Eckel RH. Lipoprotein Lipase in the a molecular target for diabetic therapy.
Wang R, Cruciani-Guglielmacci C, Migrenne Physiol Regul Integr Comp Physiol 2003; 285: Zhang M, Gosnell BA, Kelley AE. Intake of high-fat food is selectively enhanced by mu effects of oleic-acid (OA) on distinct popula- opioid receptor stimulation within the nucle- tions of neurons in the hypothalamic arcuate nucleus (ARC) are dependent on extracellular transactions of the Royal Society of London glucose levels. J Neurophysiol 2005.
Series B Biological sciences 2006; 361: 1149-58.
Zhang M, Kelley AE. Opiate agonists micro- Wilson JD, Nicklous DM, Aloyo VJ, Simansky injected into the nucleus accumbens enhance KJ. An orexigenic role for mu-opioid recep- tion of opioid receptors in the rat brainstem.
sucrose drinking in rats. Psychopharmacology tors in the lateral parabrachial nucleus. Am J

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