Chronic pramlintide decreases feeding via a reduction in meal size in male rats.

Amylin, a pancreatic hormone, is well-established to suppress feeding by enhancing satiation. Pramlintide, an amylin analog that is FDA-approved for the treatment of diabetes, has also been shown to produce hypophagia. However, the behavioral mechanisms underlying the ability of pramlintide to suppress feeding are unresolved. We hypothesized that systemic pramlintide administration in rats would reduce energy intake, specifically by reducing meal size. Male rats were given b.i.d. administration of intraperitoneal pramlintide or vehicle for 1 week, and chow intake, meal patterns, and body weight were monitored throughout the test period. Consistent with our hypothesis, pramlintide decreased chow intake mainly via suppression of meal size, with corresponding reductions in meal duration on several days. Fewer effects on meal number or feeding rate were detected. Pramlintide also reduced weight gain over the 1-week study. These results highlight that the behavioral mechanisms by which pramlintide produces hypophagia are similar to those driven by amylin itself, and provide important insight into the ability of this pharmacotherapy to promote negative energy balance over a period of chronic administration.

The alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 reduces food intake in male rats.

Obesity is a prevalent disease, but effective treatment options remain limited. Agonists of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) promote negative energy balance in mice, but these effects are not well-studied in rats. We tested the hypothesis that central administration of the α7nAChR agonist PHA-543613 (PHA) would decrease food intake and body weight in adult male Sprague Dawley rats. Intracerebroventricular (ICV) PHA administration in chow-fed rats produced a suppression of energy intake and weight gain over 24 h. Next, to evaluate effects of ICV PHA on palatable food intake, rats were maintained on a choice diet of rodent chow and 45 % high fat diet (HFD); under these conditions, ICV PHA produced no significant changes in energy intake from either food, or body weight gain, in the 24 h post-injection. However, when given a choice of chow or a higher-fat 60 % HFD, ICV PHA reduced intake of 60 % HFD, but not chow; body weight gain was also suppressed. Further experiments evaluating conditioned taste avoidance (CTA) and pica in response to ICV PHA suggested that the suppressive food intake and body weight effects after ICV injection of PHA were not due to nausea/malaise. Finally, an operant conditioning study showed that responding on a progressive ratio schedule of reinforcement for high-fat food pellets decreased after ICV PHA. Collectively, these studies show that PHA reduces energy intake under some but not all dietary conditions. Importantly, central PHA decreases both food intake as well as motivation for highly palatable, energy dense foods in rats without inducing nausea/malaise, suggesting that the α7nAChR could be a viable target for developing treatments for obesity.

Macronutrient intake: Hormonal controls, pathological states, and methodological considerations.

A plethora of studies to date has examined the roles of feeding-related peptides in the control of food intake. However, the influence of these peptides on the intake of particular macronutrient constituents of food - carbohydrate, fat, and protein - has not been as extensively addressed in the literature. Here, the roles of several feeding-related peptides in controlling macronutrient intake are reviewed. Next, the relationship between macronutrient intake and diseases including diabetes mellitus, obesity, and eating disorders are examined. Finally, some key considerations in macronutrient intake research are discussed. We hope that this review will shed light onto this underappreciated topic in ingestive behavior research and will help to guide further scientific investigation in this area.

The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 does not affect food intake in rats.

Obesity is a prevalent disease, but effective treatments remain limited. Agonists of the alpha-7 nicotinic acetylcholine receptor (α7nAChR) promote negative energy balance in mice, but these effects are not well-studied in rats. We tested the hypothesis that the α7nAChR agonist GTS-21 would decrease food intake and body weight in adult male Sprague Dawley rats. Contrary to our hypothesis, acute systemic administration of GTS-21 produced no significant effects on chow or high-fat diet (HFD) intake. Acute intracerebroventricular (ICV) GTS-21 also had no impact on chow intake, and actually increased body weight at the highest dose tested. Previous studies suggest that GTS-21 engages the food intake-suppressive glucagon-like peptide-1 (GLP-1) system in mice. As there are known species differences in GLP-1 physiology between mice and rats, we tested the ability of GTS-21 to elicit GLP-1 secretion in rats. Our results showed that plasma levels of total GLP-1 in rats were not significantly altered by peripheral GTS-21 injection. These results represent an advance in understanding how α7nAChR activation impacts energy balance control in rodents and suggest that there may be important differences between rats and mice in the ability of GTS-21/α7nAChR activation to increase secretion of GLP-1.

The impact of binge-like palatable food intake on the endogenous glucagon-like peptide-1 system in female rats.

Binge eating involves consumption of large amounts of food and a loss of control over the amount consumed. The incidence of binge eating disorder is higher in females than males, hinting at important sex differences in binge eating behavior, but the neural underpinnings of binge eating still remain unresolved. Recent work in male rats has shown that a history of binge-like palatable food intake suppresses hindbrain expression of preproglucagon (PPG), the precursor for glucagon-like peptide-1 (GLP-1). Given the roles of GLP-1 in reducing feeding and food reward, this could be a mechanism underlying binge-like eating in rodents. However, whether similar effects occur in female rats is unknown. Here, we tested the hypothesis that a history of binge-like palatable food intake in female rats would reduce PPG expression in the nucleus tractus solitarius (NTS), a key central site of GLP-1 production. Female rats given access to vegetable shortening every fourth day (4D) engaged in binge-like feeding, demonstrated by consuming significantly more shortening during the first hour of fat access compared to counterparts with ad libitum (AL) fat access. After several weeks of fat access under these schedules, PPG and GLP-1 receptor (GLP-1R) expression were measured in the NTS and ileum. Surprisingly, and in contrast to previous findings in male rats, there were no significant differences in expression of PPG or GLP-1R in either site in 4D versus AL rats, nor were there effects on plasma GLP-1 levels. These findings highlight key differences in the effects of binge-like intake on the central GLP-1 system in female compared to male rats.

Effects of pramlintide on energy intake and food preference in rats given a choice diet.

Amylin is a peptide hormone involved in the control of energy balance, making the amylin system a potential target for pharmacotherapies to treat obesity. Pramlintide, an amylin analogue, is an FDA-approved medication for the treatment of diabetes that also has food intake- and body weight-suppressive effects. However, it is unknown whether pramlintide may preferentially reduce intake of highly palatable, energy dense food, the overconsumption of which is thought to play a role in the etiology of obesity. Here, we investigate the effects of pramlintide on food intake and body weight in rats given a choice of chow and high fat diet (HFD). Systemic pramlintide injection in rats reduced HFD intake at 3h post-injection, with no effects at other times and no significant effects on chow intake, body weight, or percent preference for HFD. In a separate experiment, the effects of central injection of pramlintide on food intake and body weight were similarly evaluated. Intracerebroventricular pramlintide significantly reduced HFD intake throughout the 24h post-injection, with some suppressive effects on chow intake, and also decreased 24h body weight change. Again, no significant changes were observed in the proportion of calories obtained from HFD. The same intracerebroventricular doses of pramlintide did not induce pica, suggesting that pramlintide-mediated reductions in feeding are not due to nausea/malaise. Our results suggest that pramlintide reduces food intake in rats largely via reductions in intake of HFD versus chow, supporting the idea that the potent effects of pramlintide on palatable food intake may have utility in the treatment of obesity.