Insulin, leptin, and food reward: update 2008

Abstract

The hormones insulin and leptin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis at medial hypothalamic sites. In a previous review, we described new research demonstrating that, in addition to these direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and motivation is also a direct and an indirect target for insulin and leptin action. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, i.e., midbrain dopamine and opioidergic pathways. Here we summarize new behavioral, systems, and cellular evidence in support of this hypothesis and in the context of research into the homeostatic roles of both hormones in the CNS. We discuss some current issues in the field that should provide additional insight into this hypothetical model. The understanding of neuroendocrine modulation of food reward, as well as food reward modulation by diet and obesity, may point to new directions for therapeutic approaches to overeating or eating disorders. motivation; food intake; dopamine

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

“…Considering the involvement of insulin in cognitive and motivational processes that depend on DA neurotransmission, insulin receptors and their downstream substrates (IRS-2 and PI3K) in rat brain are densely expressed in DA neurons within the ventral tegmental area (VTA) and activation of these receptors enhances PI3K activity and DAT mRNA expression (Figlewicz et al, 1994;Pardini et al, 2006;Figlewicz and Benoit, 2009). Moreover, insulin receptor activation appeared to increase the surface expression and function of DAT in rat striatum, enhancing DA reuptake in a P13K-dependent manner (Patterson et al, 1998;Carvelli et al, 2002;Garcia et al, 2005;Lute et al, 2008).…”

“…These tyrosine kinase receptors are enriched in neurons and found in cell bodies and nerve terminal membranes of neurons in hypothalamic and higher limbic regions (Marks et al, 1988;Schulingkamp et al, 2000). Accordingly, insulin not only acts at hypothalamic sites as regulator of energy homeostasis in the periphery, but may also modulate cognitive performance and motivation (Kern et al, 2001;Zhao and Alkon, 2001;Figlewicz and Benoit, 2009). Notably, neuronal activity in the brain evoked by a peripheral insulin injection was attenuated in nondiabetic humans with peripheral insulin resistance, being most marked in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC).…”

“…Regarding the role of insulin in the behavioral effects of natural reinforcers and addictive drugs, the hormone appeared to acutely enhance the clearance of synaptically released dopamine (DA) by increasing the cell surface expression and/or function of the DA transporter (DAT) in DA nerve terminals (Patterson et al, 1998;Owens et al, 2005;Williams et al, 2007;Lute et al, 2008;Figlewicz and Benoit, 2009). Since DAT is a major target for amphetamine and cocaine (Giros et al, 1996;Rothman and Baumann, 2003), insulin receptors might therefore play a role in the cognitive and/or motivational effects of psychostimulants.…”

“…For instance, regarding motivation for food, intraventricular insulin (and leptin) application in rats appeared to reverse place preference conditioned with a high-fat diet (Figlewicz et al, 2004) and to reduce sucrose self-administration . Moreover, considering the prevalence of obesity and type 2 diabetes, a high-fat diet and genetic obesity is known to cause insulin resistance in rat brain attenuating the central inhibitory effect of insulin on food intake (Figlewicz and Benoit, 2009). Since peripheral insulin resistance in nondiabetic humans appears to be associated with attenuated insulin-evoked responses in the brain (Anthony et al, 2006), it is possible that individuals with insulin resistance are at risk of obesity because of altered functioning of the insulinsensitive mesocorticolimbic system and its progressive dysregulation upon consumption of highly palatable foods.…”

Reward Ideas and Strategies

“…Of course extra-reward are also: spending time with pets, enjoying with family, caring of babies, having fun in our hobbies, and also cultivating our mind and soul with any religious practice we can need [23][24][25][26].…”