High on food: the interaction between the neural circuits for feeding and for reward

Liu, Jingjing; Mukherjee, Diptendu; Haritan, Doron; Ignatowska‐Jankowska, Bogna M.; Liu, Ji; Citri, Ami; Pang, Zhiping P.

doi:10.1007/s11515-015-1348-0

Cited by 13 publications

(21 citation statements)

References 134 publications

(176 reference statements)

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“…Leptin suppresses excitatory synaptic drive onto LHA-to-VTA-projecting orexin and MCH neurons We used an established retrograde tracing approach (Katz et al, 1984;Köbbert et al, 2000;Lammel et al, 2008;Brown and Hestrin, 2009) to label LHA neurons forming synapses within the VTA. Briefly, we injected microfluorescent RetroBeads into the VTA and identified retrograde labeled neuronal cell bodies in the LHA (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The LHA has been recognized as a "feeding center" and is positioned to integrate energy status and metabolic signals to control food intake (Hoebel and Teitelbaum, 1962;Grossman et al, 1978;Jennings et al, 2013;Sheng et al, 2014). It is well established that LHA neurons are major targets for central leptin signaling (Leinninger et al, 2009(Leinninger et al, , 2011Domingos et al, 2013;Goforth et al, 2014;Laque et al, 2015), and it has been suggested that they may play a role in regulating the reward-associated ventral tegmental area (VTA) dopaminergic (DA) signaling and reward (Harris et al, 2005;Borgland et al, 2006;Narita et al, 2006;Leinninger et al, 2009;Domingos et al, 2013;Sheng et al, 2014). However, the complex wiring pattern and neuronal heterogeneity of the LHA (Liu et al, 2015;Mickelsen et al, 2017) has complicated the discovery of precise neural mechanisms mediating leptin function.…”

Section: Significance Statementmentioning

confidence: 99%

“…Synaptic modulation by leptin in defined neuronal circuitries, particularly in the LHA-to-VTA projection pathway, has not been previously studied. Interestingly, both orexin and MCH receptors are expressed in the VTA (Hervieu et al, 2000;Marcus et al, 2001;Saito et al, 2001;Korotkova et al, 2003). Therefore, it is conceivable that the LHA-to-VTA-projecting orexin and MCH neurons could influence VTA DA neuronal function and hence mediate the function of leptin in motivated and reward-associated food intake.…”

Section: Significance Statementmentioning

confidence: 99%

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Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus–Ventral Tegmental Area Neurocircuitry Depends on Energy State

2017

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Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states. The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food deprivation and excessive storage of energy by high-fat diet feeding dampen the suppressive effect of leptin on synaptic transmission. Together, these data show that leptin regulates synaptic transmission and might be important for maintaining energy homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Significance Statementmentioning

confidence: 99%

Section: Significance Statementmentioning

confidence: 99%

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Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus–Ventral Tegmental Area Neurocircuitry Depends on Energy State

2017

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“…Feeding behavior is ultimately determined by a complex interaction between the two (Liu et al, 2015). Hedonic eating has become a key cause of weight gain and obesity.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, there is a pressing need to further investigate the role of reward circuitry in the regulation of feeding behavior (Volkow et al, 2011). The neural circuits governing food intake intertwine with those mediating reward, and the midbrain dopaminergic (DA) system has been suggested to play a pivotal role in the regulation of reward-related behaviors, including eating (Liu et al, 2015; Volkow et al, 2011). Several studies report that pharmacologic manipulations of GLP-1 signaling, i.e., using GLP-1 analogue Exendin 4 (Exn4) or GLP-1R blocker Exendin 9 (Exn9) infusions, in the VTA (Dickson et al, 2012; Mietlicki-Baase et al, 2013), NAc (Alhadeff et al, 2012; Dossat et al, 2013; Dossat et al, 2011), NTS (Alhadeff and Grill, 2014) and the hippocampus (Hsu et al, 2015), affect the appetitive and motivational aspects of feeding.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons

et al. 2015

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SUMMARY Glucagon-like peptide-1 (GLP-1) and its analogs act as appetite suppressants and have been proven to be clinically efficacious in reducing body weight in obese individuals. Central GLP-1 is expressed in a small population of brainstem cells located in the nucleus tractus solitarius (NTS), which project to a wide range of brain areas. However, it remains unclear how endogenous GLP-1 released in the brain contributes to appetite regulation. By using chemogenetic tools, we discovered that central GLP-1 acts on the midbrain ventral tegmental area (VTA) and suppresses high-fat food intake. We used integrated pathway tracing and synaptic physiology to further demonstrate that activation of GLP-1 receptors specifically reduces the excitatory synaptic strength of dopamine (DA) neurons within the VTA that project to the nucleus accumbens (NAc) medial shell. These data suggest that GLP-1 released from NTS neurons can reduce highly palatable food intake by suppressing mesolimbic DA signaling.

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C‐section birth increases offspring obesity risk dependent on maternal diet and obesity status in rats

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et al. 2021

Obesity

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Objective The gut microbiota is a complex ecosystem that shapes host metabolism, especially in early life. Maternal vaginal and gut microbiota is vertically transmitted to offspring during natural birth. Offspring born by cesarean section (CS) do not receive these bacteria and exhibit higher obesity risk later in life. The objective of this study was to examine differences in obesity risk between offspring born naturally (NB) or by CS to lean/obese dams. Methods Lean and obese rat dams gave birth to offspring naturally or by CS. Offspring obesity risk was analyzed via body weight/composition, food intake, sucrose preference, gut microbiota, and gene expression in gut and brain tissues. Results Obese (O)+CS offspring showed greater weight gain and caloric intake but a reduction in hypothalamic agouti related neuropeptide, neuropeptide Y, and interleukin 1β expression compared with O+NB offspring. Lean (L)+CS offspring had higher serum corticosterone concentration and reduced liver peroxisome proliferator‐activated receptor γ expression compared with L+NB. O+CS offspring had long‐term alterations to gut microbiota, including increased relative abundance of Faecalibaculum and reduced Muribaculaceae. Conclusions Overall, CS alters obesity risk differentially based on maternal obesity status. Further studies looking at the risks of obesity associated with CS are needed, with special attention paid to maternal obesity status and gut microbiota.

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High on food: the interaction between the neural circuits for feeding and for reward

Cited by 13 publications

References 134 publications

Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus–Ventral Tegmental Area Neurocircuitry Depends on Energy State

Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus–Ventral Tegmental Area Neurocircuitry Depends on Energy State

Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing Synaptic Drive onto Mesolimbic Dopamine Neurons

C‐section birth increases offspring obesity risk dependent on maternal diet and obesity status in rats

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