Chronic calorie‐dense diet drives differences in motivated food seeking between obesity‐prone and resistant mice

Abstract

Obesity results from overconsumption of energy, partly because of the inability to refrain from highly palatable rewarding foods. Even though palatable food is available to everyone, only a fraction of the population develops obesity. We previously showed that following chronic exposure to highly palatable food animals that gained the most weight also showed addictive-like motivation to seek for palatable food. An important question remains-is this extreme, addictive-like, motivation to consume palatable food the cause or the consequence of diet-induced obesity? Here, we show that obesity-prone (OP) mice exhibit higher motivation for palatable food consumption compared with obesity-resistant mice even before developing obesity, but that the full manifestation of this high motivation to eat is expressed only after chronic exposure to high-fat-high-sugar (HFHS) diet. HFHS diet also impairs performance in the operant food-seeking task selectively in OP mice, an impairment that persists even after 2 weeks of abstinence from HFHS food. Overall, our data suggest that while some aspects of food motivation are high in OP mice already before developing obesity, the chronic exposure to HFHS food accentuates it and drives the development of obesity.

Metaplasticity in the ventral pallidum as a potential marker for the development of diet-induced obesity

“…Note that there was no correlation between the head entries and the lever presses ( Figure 5C), confirming our previous finding that prior to the chronic consumption of HFHS diet head entries may be a better predictor of future weight gain than operant food seeking (20).…”

“…Lastly, we were able to identify the tendency to show long term potentiation in the VP as a possible innate marker for excessive gain of weight when chronically 9 exposed to HFHS diet. In a previous study we showed that OP mice seek for palatable food more intensely (higher head entries to the food receptacle) than OR mice even before being exposed to chronic HFHS diet (20). Thus, we used here the intensity of food seeking in HFHSnaive mice as a possible marker for future weight gain.…”

“…In a recent study (20) we showed that in a progressive ratio task where the reward is a small pellet of HFHS food, head entries to the food receptacle may serve as a good predictor for being prone to develop obesity (20). Accordingly, mice that eventually were defined as OP mice showed significantly more head entries than OR mice even when the test was conducted before the beginning of the HFHS diet.…”

“…Previous studies showed that not only does weight gain correlate with addiction-like behaviors towards palatable food (14,15,20), it also correlates with synaptic changes in the NAc (14, 15) -OP rats show stronger excitatory input to the NAc compared to OR rats. As the VP is a major target of the NAc, we expect that the physiology of the VP will also differ between OP and OR mice.…”

“…Thus, the expression level of the dopamine receptor D2/3 in the striatum is decreased in obese humans (7)(8)(9) and rodents (6,10); opioid signaling in both the ventral tegmental area (VTA) (11,12), and the nucleus accumbens (NAc) (12,13) is altered in obese rodents; and the glutamatergic input to the NAc is potentiated in rats that develop diet-induced obesity (14,15), akin to the effect seen after withdrawal from cocaine (16,17) or nicotine (16,18). Possibly as a consequence of these changes in the reward system, rats and mice that gain the most weight in a diet-induced obesity model also show the highest motivation to obtain palatable food (10,14,(19)(20)(21).…”