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Issue
OCL
Volume 22, Number 4, July-August 2015
Article Number D407
Number of page(s) 6
Section Dossier: 12th Euro Fed Lipids Congress: Oils, Fats and Lipids: From Lipidomics to Industrial Innovation
DOI https://doi.org/10.1051/ocl/2015013
Published online 01 May 2015

© C. Cansell and S. Luquet, Published by EDP Sciences, 2015

Licence Creative Commons This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1 Introduction

Between 1980 and 2008 the mean BMI of the world’s population has increased dramatically. Globally, in 2008, around 35% of adults aged 20 and over were overweight and around 12% were obese (World Health Organization (WHO) estimations). Obesity is a risk factor for chronic diseases like cardiovascular diseases, diabetes, degenerative joint diseases and cancers. Overweight and obesity are the fifth worldwide mortality factor (WHO estimation). Monogenic form of obesity shows that genetic factors can be involved in the establishment of this disease (Xia and Grant, 2013). However in many case, obesity results from interaction between genetic predisposition and negative environment. In fact, maintenance of a healthy body weight is possible through a fine regulation of energy balance which coordinates energy intake, food consumption, and energy release, activity and thermogenesis. In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance, and consequently, excessive caloric intake and reduced energy expenditure are the main causes for the prevalence of obesity (Hill et al., 2003). The central regulator of food intake and energy expenditure is the brain and particularly the hypothalamus which is the primary site of circulating energy-related signals integration like leptin, ghrelin, or lipids and glucose (Schwartz and Porte, 2005). Imbalance in this regulatory process invariably leads to metabolic diseases such as obesity and diabetes in both humans and rodent models (Denis et al., 2014; Schwartz and Porte, 2005). Especially, hypothalamus lipids sensing has emerged as a key component in brain regulation of energy balance (Blouet and Schwartz, 2010; Moulle et al., 2014). Alteration of hypothalamic lipid sensing appears to be involved in several brain response to nutrient oversupply (i.e. inflammation, ER stress...) that leads to obesity (Velloso and Schwartz, 2011). Food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. For example, stress or anxiety can stimulate reward seeking and consumption of highly palatable food independent of metabolic demand (Dallman et al., 2003). Among several brain circuits, the mesolimbic pathway is well established as a main actor of the rewarding aspect of feeding. In fact, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). DA release is stimulated by high-fat/ high-sugar (HFHS) foods as well as by various desirable stimuli (e.g., sex, drugs) (Palmiter, 2007; Volkow et al., 2011; Wise, 2006). HFHS diet consumption in both human and rodent has been associated with the progressive loss in spontaneous locomotor activity, and it has been shown that an acute reduction in locomotor activity is a major contributor to western diet-induced obesity in mice (Bjursell et al., 2008). Moreover HFHS diet were also link to the establishment of an addictive-like reward dysfunction and compulsive eating in obese rats (Johnson and Kenny, 2010) and depressive like behaviour (Hryhorczuk et al., 2013). Interestingly, obesity-associated cognitive impairment can be improved by selective lowering of circulating triglyceride (TG) (Farr et al., 2008). Altogether, those observations raise the possibility that nutritional lipids, and specifically triglycerides, directly act on brain structure-through mechanism similar as hypothalamic lipid sensing to affect cognitive and reward processes and contribute to the downward spiral of compulsive food consumption.

In this review, we will focus on mechanism by which brain regulates rewarding component of food intake and then expose recent evolution in the field that might point toward a direct action of nutritional lipid in the mesolimbic pathway.

2 Hedonic and motivational aspect of feeding: a focus on the mesolimbic pathway

Hypothalamic integration of orexigenic and anorexigenic circulating signals allow the brain to adapt food intake according to energy needs, however, the food palatability is a powerful determinant of feeding and characterize the rewarding aspect of food intake. Palatability defines food properties which induce animal sensitive response for this food and so induce a desire more or less important for this food (Greenhalgh and Reid, 1971). Food palatability is characterized by the smell, the taste, the texture, the temperature and the appearance of the food. Nevertheless, it is not only an inherent property of food as it is also defined by experience, metabolic demands and other environmental factors like stress (de Castro et al., 2000). The mesolimbic pathway is one of neural networks which encode the different aspect of food intake: “liking”, “wanting” and “learning” (Berridge, 2009; Wise, 2006). The mesolimbic pathway is a dopaminergic pathway. Although, DA is a neurotransmitter well studied in reward processes, opioids, endocannabinoids, serotonin and others are also involved in the rewarding aspect of food intake but we will not discuss it in this review (Kelley et al., 2002; Le Merrer et al., 2009). It has been shown that DA antagonists increase appetite, energy intake and weight gain, whereas DA agonists reduce energy intake and produce weight loss (Leddy et al., 2004; de Leon et al., 2007). DA binds to several G-protein-coupled DA receptors-D1 and D5 coupled to Gsα; D2, D3 and D4 coupled to Giα-which activate intracellular signalling pathways in postsynaptic neurons. DA neurons are mainly located in the Ventral Tegmental Area (VTA) and innervate limbic regions like the Nacc, the prefrontal cortex (PFC), the amygdala (AG) and the hippocampus (HP). During regular circumstances, DA neurons are firing continuously causing tonic DA release; salient environmental stimuli induce burst-firing of DA neurons resulting in a burst of DA release (Palmiter, 2007). Palatable food ingestion is associated with DA release in Nacc, and the degree of pleasure from eating correlates with amount of DA released (Small et al., 2003; Szczypka et al., 2001). DA is also involved with the motivation to perform behaviours necessary to procure and consume the food. In fact, DA-deficient mice are hypophagic, fail to engage in goaldirected feeding behaviours, and will die of starvation (Palmiter, 2008; Szczypka et al., 1999). Moreover, it was found that chemical lesions of the DA system (pharmacological antagonists of DA receptor), sufficient to inhibit food-seeking behaviour, did not affect the pleasure reactions to sucrose placed in the mouth (Berridge and Robinson, 1998; Tyrka et al., 1992). This finding was interpreted as indicating that the neural systems mediating the pleasure impact of preferred tastes was distinct from that mediating the ability of incentives to elicit goal-directed behaviour; these two processes were termed “liking” and “wanting”, respectively. With regard to neurochemical mediation, it was proposed that “wanting” is governed by DA whereas “liking” depends upon opioid transmission (Kelley et al., 2005).

In summary the rewarding aspect of food intake elicited by the mesolimbic pathway activation is well established as a main actor of feeding regulation however the neurochemical characterization of this process is still discussed (Maldonado et al., 2006; Palmiter, 2007; Will et al., 2006).

3 Mesolimbic lipid sensing and feeding behaviour

3.1 Brain lipid sensing

Cerebral lipids are an essential component of both membranes and intracellular signalling pathways. They represent 50% of brain dry weight – the highest organ lipid content after adipose tissue (Edmond, 2001; Watkins et al., 2001). A growing body of evidence suggests that cerebral lipids are derived from both local synthesis and uptake from the blood. In fact, in human, brain signal of radiolabelled arachidonic acid (AA) has been shown by Positron Emission Tomography (PET) scan imaging following the intravenous injection of radiolabeled AA (Esposito et al., 2007). PET scan imaging also demonstrates Palmitate and AA brain incorporation in primate and rats (Arai et al., 1995; Chang et al., 1997a, 1997b). Although their transport mechanism across the BBB are still not clear, several studies show that some polyunsaturated FA (PUFA) have the ability to cross the BBB (Rapoport et al., 2001; Smith and Nagura, 2001). Once across the BBB, it is probable that neurons can take up FA as some neurons do appear to have FA transporters. For example, dissociated neurons from the hypothalamic ventromedial nucleus (VMN) of rats express mRNAs for FA transport proteins (FATP)-1 and 4, and the FA transporter/receptor FAT/CD36 mRNAs (Le Foll et al., 2009, 2013). Lipoproteins are also a major source of lipids for the brain (Giovacchini et al., 2002) and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) transport across the BBB has been demonstrated in vitro (Balazs et al., 2004; Candela et al., 2008) and in vivo in Drosophila (Brankatschk and Eaton, 2010). Regarding their transport mechanism it has been suggested that lipoproteins could be detected by specific receptors in endothelial cells and then transported and metabolised in the brain (Chen et al., 2008; Edmond, 2001). Another model suggests that TG contained in lipoproteins could be hydrolysed at the level of BBB by the LPL; liberated FA could then be transported in the brain (Chen et al., 2008; Rapoport, 2001) via passive transport, the flip-flop (Mitchell and Hatch, 2011) or active transport via transport proteins described above (Mitchell and Hatch, 2011).

Hypothalamic lipid sensing is involved in the central regulation of different aspect of energy balance like food intake, pancreatic hormones secretion, hepatic glucose production, lipids metabolism and energy expenditure (Blouet and Schwartz, 2010; Moulle et al., 2014; Picard et al., 2014). Most of studies about brain lipid sensing focused on FA, however TG are also involved in the central regulation of energy balance. In fact, TG are able to change BBB permeability to Ghrelin and so participates to the regulation of food intake (Kumar et al., 2002). Moreover a recent study has shown that the central inhibition of TG hydrolysis by the LPL induces hyperphagia and obesity (Wang et al., 2011). Although fatty acid have been shown to regulate food intake through hypothalamic network (Lam et al., 2005) it must be pointed out that, unlike plasma TG-rich lipoproteins which rise after a meal, plasma level of FA actually decrease due to the combined action of lipolysis inhibition and hyperinsulinemia (Ruge et al., 2009). Indeed, during a meal the hydrolysis and absorption by the gut leads to TG packaging and finally chylomicrons synthesis. Moreover the liver also produces very low density lipoprotein (VLDL). Thus TG-rich lipoproteins, accumulating after a meal, could also pretend to be a physiologically relevant satiety signal acting in the brain to regulate feeding behaviour and energy expenditure (Blouet and Schwartz, 2010; Migrenne et al., 2011; Wang et al., 2011).

3.2 Mesolimbic triglycerides sensing

Both mesolimbic and hypothalamic regions express enzymes involved in the transport, manipulation and metabolism of TG (Eckel and Robbins, 1984; Kim et al., 2002; Paradis et al., 2004; Rapoport, 2001; Ronnett et al., 2005, 2006; Wang and Eckel, 2009, 2012). In particular, the HP and the Nacc express LPL, a key enzyme involved in TG hydrolysis (Ben-Zeev et al., 1990). Recent studies have highlighted the importance of brain TG hydrolysis in the regulation of energy balance (Wang et al., 2011). In fact neuronal deletion of LPL induces hyperphagia, energy expenditure and locomotor activity decrease, and finally obesity in mice on standard diet (Wang et al., 2011). Moreover variation in circulating TG after a high-fat meal is a strong predictor for hyperphagia and obesity (Karatayev et al., 2009) but until now a physiological model that allows for the study of TG action on the brain has been missing. In a recent study we have established a method to evaluate the behavioural and metabolic consequences of brain TG sensing by infusing TG via the natural route of access to the brain through the carotid artery in the direction of the brain, at a rate and concentration that closely recapitulate the postprandial increase in TG but without affecting systemic FA or TG concentrations. Our results provide the first experimental evidence that TG can directly target mesolimbic structures to modulate the rewarding component of food intake (Cansell et al., 2014). Such TG infusion leads to a decrease in nocturnal and amphetamine (DA activator) induced locomotor activity and abolishes preference for palatable HFHS food in lean mice. As described before, the palatable property of food and its ability to induce pleasure are regulated by the reward system and particularly involved DA signalling. The action of central TG delivery on food preference, nocturnal activity and psychostimulant- induced locomotion suggested that brain TG signalling may directly influence motivated behaviour. We tested this hypothesis by first pretraining mice to lever press for high sucrose food reward pellets, and then following intra-carotid saline or TG infusion, assessing their performance on a Progressive Ratio (PR) task that measures the amount of effort an animal is willing to exert to obtain food rewards. We demonstrated that brain TG delivery decreases the overall motivation to work for reward. We have also begun to define the neural circuitry and molecular mechanisms by which TG influence neural activity and behaviour. Indeed, in contrast to the effects of TG infusion, deletion of the gene encoding the TG-hydrolyzing enzyme LpL specifically in the Nacc leads to sensitization to the reinforcing properties of palatable food as revealed by the PR operant task and hyperphagia during a HFHS food preference task (Cansell et al., 2014).

As previously enounced, plasma TG accumulate after a meal and gradually return to basal levels (Ruge et al., 2009). However, plasma TG is often chronically elevated in obesity (Subramanian and Chait, 2012). During prolonged TG perfusion, designed to mimic chronic hypertriglyceridemia, we found that adaptive desensitization processes occur such that TG infusion no longer abolishes HFHS preference but continues to suppress locomotor activity. Consistent with this, using Diet Induced Obesity (DIO) mice to physiologically model chronic hypertriglyceridemia, central TG delivery still reduced locomotor activity but no longer was effective in modulating food preference. Together, these data suggest a model whereby postprandial increases in plasma TG are hydrolyzed locally in the Nacc where they alter the reward system to effect a reduction in locomotor activity and reduce the incentive properties of calorie-rich HFHS foods. Those findings are consistent with a recent study demonstrating that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and TG (Sun et al., 2014). However, in the face of sustained elevations in plasma TG, achieved either by intra-carotid perfusion or DIO, the mechanisms that normally serve to reduce the rewarding impact of HFHS foods is no longer operating (Cansell et al., 2014). This model predicts a positive feedback loop whereby chronically high plasma TG, such as occurs in obesity, cripple the homeostatic mechanisms that curb food intake resulting in uncontrolled caloric consumption and reduced physical activity. Such a mechanism would serve to drive body weight gain, whereas making weight loss more difficult. Further studies will be required to uncover the cellular basis of mesolimbic TG sensing mediated by LPL, the downstream molecular events that occur following TG hydrolysis, and how these events alter the activity of rewarding circuits.

4 Conclusion

Previous work on how circulating lipids affect the brain has focused chiefly on the effects of FA on brain metabolism and behavior. For instance, intracerebroventricular injection of oleic acid was shown to alter hypothalamic lipid metabolism and result in decreased food intake (Obici et al., 2002). Furthermore, lipid metabolism in the hypothalamus has been repeatedly shown to be critical in mediating the central effects of FA (Lam et al., 2005; Moulle et al., 2014; Picard et al., 2014). We therefore propose that the central availability of TG and FA differ (Fig. 1), that these lipid species influence neural circuit function through separate mechanisms, and that they have opposing effects on food-seeking behaviour. Although FA may principally act in the hypothalamus and function to increase food intake in response to a fast, TG sensing may depend on local hydrolysis by LpL in the mesolimbic pathway where they decrease the rewarding or motivational properties of food. Potential mechanisms could involve lipid-mediated activation of membrane receptors (Abumrad et al. 2005; Moulle et al., 2013) cellular energy-related pathways (Lage et al., 2008; Lopez et al., 2005) endoplasmic reticulum stress (Zhang et al., 2008) eicosanoids-dependent inflammatory processes (Rapoport et al., 2001), endocannabinoid signalling pathways (Lafourcade et al., 2011; Solinas et al., 2008) and lipid-activated transcriptional adaptations (Aleshin et al., 2013).

thumbnail Fig. 1

Brain nutritional lipids sensing and the central regulation of energy balance. We therefore propose that the central availability of TG and FA differe, that these lipid species influence neural circuit function through separate mechanisms, and that they have opposing effects on food-seeking behaviour. Although FA may principally act in the hypothalamus and function to increase food intake in response to a fast, TG sensing may depend on local hydrolysis by LpL in the mesolimbic pathway where they decrease the rewarding or motivational properties of food. Amy, amygdala; ARC, arcuate nucleus; Cpu, caudate putamen; DMH, dorsomedial hypothalmaus; HP, hippocampus; LH, lateral nucleus; LPL, Lipoprotein lipase; Nacc, nucleus accumbens; NTS, nucleus tractus solitarius; PFC, prefrontal cortex; PVN, para-venticular nucleus; SN, substantia nigra; VMH, ventromedial hypothalamus; VTA, ventral tegmental area.

It has been shown that hypothalamic FA sensing is involved in the central regulation of food intake and glucose homeostasis. In a recent study we demonstrated that TG acts on the mesolimbic pathway probably through a mechanism dependant on their hydrolysis by LPL (Lam et al., 2005; Moulle et al., 2014; Picard et al., 2014).

The authors declare no conflict of interest.

Acknowledgments

Ideas discussed here are based in part on a presentation of the author at the 12th Euro Fed Lipid Congress. This work as supported by ATIP grant from the “Centre National de la Recherche Scientifique” (CNRS) and by the “Agence Nationale de la Recherche” (ANR -09-BLAN-0267-02 and ANR 11 BSV1 021 01). CC received a PhD fellowship from the CNRS, a research fellowship from the “Société Francophone du Diabete-Roche” (SFD) and an award from the “Groupe d’étude et de recherche en lipidomique” (GERLI).

References

  • Abumrad NA, Ajmal M, Pothakos K, Robinson JK. 2005. CD36 expression and brain function: does CD36 deficiency impact learning ability? Prostaglandins Other Lipid Mediat. 77: 77–83. [CrossRef] [PubMed] [Google Scholar]
  • Aleshin S, Strokin M, Sergeeva M, Reiser G. 2013. Peroxisome proliferator-activated receptor (PPAR)beta/delta, a possible nexus of PPARalpha- and PPARgamma-dependent molecular pathways in neurodegenerative diseases: Review and novel hypotheses. Neurochem. Int. 63: 322–330. [CrossRef] [PubMed] [Google Scholar]
  • Arai T, Wakabayashi S, Channing MA, et al. 1995. Incorporation of [1-carbon-11]palmitate in monkey brain using PET. J. Nucl. Med. 36: 2261–2267. [Google Scholar]
  • Balazs Z, Panzenboeck U, Hammer A, et al. 2004. Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J. Neurochem. 89: 939–950. [CrossRef] [PubMed] [Google Scholar]
  • Ben-Zeev O, Doolittle MH, Singh N, Chang CH, Schotz MC. 1990. Synthesis and regulation of lipoprotein lipase in the hippocampus. J. Lipid Res. 31: 1307–1313. [PubMed] [Google Scholar]
  • Berridge KC. 2009. “Liking” and “wanting” food rewards: brain substrates and roles in eating disorders. Physiol. Behav. 97: 537–550. [CrossRef] [PubMed] [Google Scholar]
  • Berridge KC, Robinson TE. 1998. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Rev. 28: 309–369. [Google Scholar]
  • Bjursell M, Gerdin AK, Lelliott CJ, et al. 2008. Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice. Am. J. Physiol. Endocrinol. Metab. 294: E251–E260. [CrossRef] [PubMed] [Google Scholar]
  • Blouet C, Schwartz GJ. 2010. Hypothalamic nutrient sensing in the control of energy homeostasis. Behav. Brain Res. 209: 1–12. [Google Scholar]
  • Brankatschk M, Eaton S. 2010. Lipoprotein particles cross the blood-brain barrier in Drosophila. J. Neurosci. 30: 10441–10447. [CrossRef] [PubMed] [Google Scholar]
  • Candela P, Gosselet F, Miller F, et al. 2008. Physiological pathway for low-density lipoproteins across the blood-brain barrier: transcytosis through brain capillary endothelial cells in vitro. Endothelium 15: 254–264. [CrossRef] [PubMed] [Google Scholar]
  • Cansell C, Castel J, Denis RG, et al. 2014. Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding. Mol. Psychiatry 19: 1095–1105. [Google Scholar]
  • Chang MC, Arai T, Freed LM, et al. 1997a. Brain incorporation of [1-11C]arachidonate in normocapnic and hypercapnic monkeys, measured with positron emission tomography. Brain Res. 755: 74–83. [CrossRef] [Google Scholar]
  • Chang MC, Grange E, Rabin O, Bell JM. 1997b. Incorporation of [U-14C]palmitate into rat brain: effect of an inhibitor of beta-oxidation. J. Lipid Res. 38: 295–300. [PubMed] [Google Scholar]
  • Chen CT, Green JT, Orr SK, Bazinet RP. 2008. Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot. Essent. Fatty Acids 79: 85–91. [Google Scholar]
  • Dallman MF, Pecoraro N, Akana SF, et al. 2003. Chronic stress and obesity: a new view of “comfort food". Proc. Natl. Acad. Sci. USA 100: 11696–11701. [Google Scholar]
  • De Castro JM, Bellisle F, Dalix AM, Pearcey SM. 2000. Palatability and intake relationships in free-living humans. characterization and independence of influence in North Americans. Physiol. Behav. 70: 343–350. [CrossRef] [PubMed] [Google Scholar]
  • De Leon J, Diaz FJ, Josiassen RC, Cooper TB, Simpson GM. 2007. Weight gain during a double-blind multidosage clozapine study. J. Clin. Psychopharmacol. 27: 22–27. [Google Scholar]
  • Denis RG, Joly-Amado A, Cansell C, Castel J, Martinez S, Delbes AS, Luquet S. 2014. Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome. Diabetes Metab. 40: 191–197. [CrossRef] [PubMed] [Google Scholar]
  • Eckel RH, Robbins RJ. 1984. Lipoprotein lipase is produced, regulated, and functional in rat brain. Proc. Natl Acad. Sci. USA 81: 7604–7607. [CrossRef] [Google Scholar]
  • Edmond J. 2001. Essential polyunsaturated fatty acids and the barrier to the brain: the components of a model for transport. J. Mol. Neurosci. 16: 181–193; discussion 215–121. [CrossRef] [PubMed] [Google Scholar]
  • Esposito G, Giovacchini G, Der M, et al. 2007. Imaging signal transduction via arachidonic acid in the human brain during visual stimulation, by means of positron emission tomography. Neuroimage 34: 1342–1351. [CrossRef] [PubMed] [Google Scholar]
  • Farr SA, Yamada KA, Butterfield DA, et al. 2008. Obesity and hypertriglyceridemia produce cognitive impairment. Endocrinology 149: 2628–2636. [CrossRef] [PubMed] [Google Scholar]
  • Giovacchini G, Chang MC, Channing MA, et al. 2002. Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography. J. Cereb. Blood Flow Metab. 22: 1453–1462. [CrossRef] [PubMed] [Google Scholar]
  • Greenhalgh JF, Reid GW. 1971. Relative palatability to sheep of straw, hay and dried grass. Br. J. Nutr. 26: 107–116. [CrossRef] [PubMed] [Google Scholar]
  • Hill JO, Wyatt HR, Reed GW, Peters JC. 2003. Obesity and the environment: where do we go from here? Science 299: 853–855. [CrossRef] [PubMed] [Google Scholar]
  • Hryhorczuk C, Sharma S, Fulton SE. 2013. Metabolic disturbances connecting obesity and depression. Front. Neurosci. 7: 177. [CrossRef] [PubMed] [Google Scholar]
  • Johnson PM, Kenny PJ. 2010. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat. Neurosci. 13: 635–641. [Google Scholar]
  • Karatayev O, Gaysinskaya V, Chang GQ, Leibowitz SF. 2009. Circulating triglycerides after a high-fat meal: predictor of increased caloric intake, orexigenic peptide expression, and dietary obesity. Brain Res. 1298: 111–122. [CrossRef] [PubMed] [Google Scholar]
  • Kelley AE, Bakshi VP, Haber SN, Steininger TL, Will MJ, Zhang M. 2002. Opioid modulation of taste hedonics within the ventral striatum. Physiol. Behav. 76: 365–377. [Google Scholar]
  • Kelley AE, Baldo BA, Pratt WE. 2005. A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward. J. Comp. Neurol. 493: 72–85. [Google Scholar]
  • Kim EK, Miller I, Landree LE, et al. 2002. Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment. Am. J. Physiol. Endocrinol. Metab. 283: E867–879. [Google Scholar]
  • Kumar MV, Shimokawa T, Nagy TR, Lane MD. 2002. Differential effects of a centrally acting fatty acid synthase inhibitor in lean and obese mice. Proc. Natl Acad. Sci. USA 99: 1921–1925. [CrossRef] [Google Scholar]
  • Lafourcade M, Larrieu T, Mato S, et al. 2011. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat. Neurosci. 14: 345–350. [CrossRef] [PubMed] [Google Scholar]
  • Lage R, Dieguez C, Vidal-Puig A, Lopez M. 2008. AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol. Med. 14: 539–549. [CrossRef] [PubMed] [Google Scholar]
  • Lam TK, Schwartz GJ, Rossetti L. 2005. Hypothalamic sensing of fatty acids. Nat. Neurosci. 8: 579–584. [Google Scholar]
  • Le Foll C, Dunn-Meynell A, Musatov S, Magnan C, Levin BE. 2013. FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice. Diabetes 62: 2709–2716. [CrossRef] [PubMed] [Google Scholar]
  • Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE. 2009. Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297: R655–664. [Google Scholar]
  • Le Merrer J, Becker JA, Befort K, Kieffer BL, 2009. Reward processing by the opioid system in the brain. Physiol. Rev. 89: 1379–1412. [Google Scholar]
  • Leddy JJ, Epstein LH, Jaroni JL, Roemmich JN, Paluch RA, Goldfield GS, Lerman C. 2004. Influence of methylphenidate on eating in obese men. Obes. Res. 12: 224–232. [Google Scholar]
  • Lopez M, Tovar S, Vazquez MJ, Nogueiras R, Senaris R, Dieguez C. 2005. Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin system. Peptides 26: 1753–1758. [CrossRef] [PubMed] [Google Scholar]
  • Maldonado R, Valverde O, Berrendero F. 2006. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 29: 225–232. [CrossRef] [PubMed] [Google Scholar]
  • Migrenne S, Le Foll C, Levin BE, Magnan C. 2011. Brain lipid sensing and nervous control of energy balance. Diabetes Metab. 37: 83–88. [CrossRef] [PubMed] [Google Scholar]
  • Mitchell RW, Hatch GM. 2011. Fatty acid transport into the brain: of fatty acid fables and lipid tails. Prostaglandins Leukot. Essent. Fatty Acids 85: 293–302. [Google Scholar]
  • Moulle VS, Le Foll C, Philippe E, et al. 2013. Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats. PLoS One 8: e74021. [CrossRef] [PubMed] [Google Scholar]
  • Moulle VS, Picard A, Le Foll C, Levin BE, Magnan C. 2014. Lipid sensing in the brain and regulation of energy balance. Diabetes Metab. 40: 29–33. [CrossRef] [PubMed] [Google Scholar]
  • Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L. 2002. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51: 271–275. [CrossRef] [PubMed] [Google Scholar]
  • Palmiter RD. 2007. Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci. 30: 375–381. [CrossRef] [PubMed] [Google Scholar]
  • Palmiter RD. 2008. Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice. Ann. N.Y. Acad. Sci. 1129: 35–46. [Google Scholar]
  • Paradis E, Clavel S, Julien P, et al. 2004. Lipoprotein lipase and endothelial lipase expression in mouse brain: regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia. Neurobiol. Dis. 15: 312–325. [Google Scholar]
  • Picard A, Moulle VS, Le Foll C, et al. 2014. Physiological and pathophysiological implications of lipid sensing in the brain. Diabetes. Obes. Metab. 16: 49–55. [CrossRef] [PubMed] [Google Scholar]
  • Rapoport SI. 2001. In vivo fatty acid incorporation into brain phosholipids in relation to plasma availability, signal transduction and membrane remodeling. J. Mol. Neurosci. 16: 243–261; discussion 279–284. [Google Scholar]
  • Rapoport SI, Chang MC, Spector AA. 2001. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J. Lipid Res. 42: 678–685. [Google Scholar]
  • Ronnett GV, Kim EK, Landree LE, Tu Y. 2005. Fatty acid metabolism as a target for obesity treatment. Physiol. Behav. 85: 25–35. [Google Scholar]
  • Ronnett GV, Kleman AM, Kim EK, Landree LE, Tu Y. 2006. Fatty acid metabolism, the central nervous system, and feeding. Obesity 14: 201S–207S. [Google Scholar]
  • Ruge T, Hodson L, Cheeseman J, et al. 2009. Fasted to fed trafficking of Fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage. J. Clin Endocrinol. Metab. 94: 1781–1788. [Google Scholar]
  • Schwartz MW, Porte D Jr. 2005. Diabetes, obesity, and the brain. Science 307: 375–379. [CrossRef] [PubMed] [Google Scholar]
  • Small DM, Jones-Gotman M, Dagher A. 2003. Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroimage 19: 1709–1715. [CrossRef] [PubMed] [Google Scholar]
  • Smith QR, Nagura H. 2001. Fatty acid uptake and incorporation in brain: studies with the perfusion model. J. Mol. Neurosci. 16: 167–172; discussion 215–121. [Google Scholar]
  • Solinas M, Goldberg SR, Piomelli D. 2008. The endocannabinoid system in brain reward processes. Br. J. Pharmacol. 154: 369–383. [CrossRef] [PubMed] [Google Scholar]
  • Subramanian S, Chait A. 2012. Hypertriglyceridemia secondary to obesity and diabetes. Biochim. Biophys. Acta 1821: 819–825. [CrossRef] [PubMed] [Google Scholar]
  • Sun X, Veldhuizen MG, Wray AE, de Araujo IE, Sherwin RS, Sinha R, Small DM. 2014. The neural signature of satiation is associated with ghrelin response and triglyceride metabolism. Physiol. Behav. 136: 63–73. [CrossRef] [PubMed] [Google Scholar]
  • Szczypka MS, Kwok K, Brot MD, Marck BT, Matsumoto AM, Donahue BA, Palmiter RD. 2001. Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice. Neuron 30: 819-828. [CrossRef] [PubMed] [Google Scholar]
  • Szczypka MS, Mandel RJ, Donahue BA, Snyder RO, Leff SE, Palmiter RD. 1999. Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice. Neuron. 22: 167–178. [CrossRef] [PubMed] [Google Scholar]
  • Tyrka A, Gayle C, Smith GP. 1992. Raclopride decreases sucrose intake of rat pups in independent ingestion tests. Pharmacol. Biochem. Behav. 43: 863–869. [Google Scholar]
  • Velloso LA, Schwartz MW. 2011. Altered hypothalamic function in diet-induced obesity. Int. J. Obes. 35: 1455–1465. [CrossRef] [PubMed] [Google Scholar]
  • Volkow ND, Wang GJ, Baler RD. 2011. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn. Sci. 15: 37–46. [Google Scholar]
  • Wang H, Astarita G, Taussig MD, et al. 2011. Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity. Cell Metab. 13: 105–113. [CrossRef] [PubMed] [Google Scholar]
  • Wang H, Eckel RH. 2009. Lipoprotein lipase: from gene to obesity. Am. J. Physiol. Endocrinol. Metab. 297: E271–288. [CrossRef] [PubMed] [Google Scholar]
  • Wang H, Eckel RH. 2012. Lipoprotein lipase in the brain and nervous system. Ann. Rev. Nutr. 32: 147–160. [CrossRef] [Google Scholar]
  • Watkins PA, Hamilton JA, Leaf A, et al. 2001. Brain uptake and utilization of fatty acids: applications to peroxisomal biogenesis diseases. J. Mol. Neurosci. 16: 87–92; discussion 151–157. [CrossRef] [Google Scholar]
  • Will MJ, Pratt WE, Kelley AE. 2006. Pharmacological characterization of high-fat feeding induced by opioid stimulation of the ventral striatum. Physiol. Behav. 89: 226–234. [CrossRef] [PubMed] [Google Scholar]
  • Wise RA. 2006. Role of brain dopamine in food reward and reinforcement. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361: 1149–1158. [Google Scholar]
  • Xia Q, Grant SF. 2013. The genetics of human obesity. Ann. N.Y. Acad. Sci. 1281: 178–190. [CrossRef] [Google Scholar]
  • Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. 2008. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135: 61–73. [CrossRef] [PubMed] [Google Scholar]

Cite this article as: Celine Cansell, Serge Luquet. Mesolimbic lipid sensing and the regulation of feeding behaviour. OCL 2015, 22(4) D407.

All Figures

thumbnail Fig. 1

Brain nutritional lipids sensing and the central regulation of energy balance. We therefore propose that the central availability of TG and FA differe, that these lipid species influence neural circuit function through separate mechanisms, and that they have opposing effects on food-seeking behaviour. Although FA may principally act in the hypothalamus and function to increase food intake in response to a fast, TG sensing may depend on local hydrolysis by LpL in the mesolimbic pathway where they decrease the rewarding or motivational properties of food. Amy, amygdala; ARC, arcuate nucleus; Cpu, caudate putamen; DMH, dorsomedial hypothalmaus; HP, hippocampus; LH, lateral nucleus; LPL, Lipoprotein lipase; Nacc, nucleus accumbens; NTS, nucleus tractus solitarius; PFC, prefrontal cortex; PVN, para-venticular nucleus; SN, substantia nigra; VMH, ventromedial hypothalamus; VTA, ventral tegmental area.

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