The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca²⁺ activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.

From anecdotal evidence that traditional African sorghum and millet foods are filling and provide sustained energy, we hypothesized that gastric emptying rates of sorghum and millet foods are slow, particularly compared to non-traditional starchy foods (white rice, potato, wheat pasta). A human trial to study gastric emptying of staple foods eaten in Bamako, Mali was conducted using a carbon-13 (¹³C)-labelled octanoic acid breath test for gastric emptying, and subjective pre-test and satiety response questionnaires. Fourteen healthy volunteers in Bamako participated in a crossover design to test eight starchy staples. A second validation study was done one year later in Bamako with six volunteers to correct for endogenous ¹³C differences in the starches from different sources. In both trials, traditional sorghum and millet foods (thick porridges and millet couscous) had gastric half-emptying times about twice as long as rice, potato, or pasta (p < 0.0001). There were only minor changes due to the ¹³C correction. Pre-test assessment of millet couscous and rice ranked them as more filling and aligned well with postprandial hunger rankings, suggesting that a preconceived idea of rice being highly satiating may have influenced subjective satiety scoring. Traditional African sorghum and millet foods, whether viscous in the form of a thick porridge or as non-viscous couscous, had distinctly slow gastric emptying, in contrast to the faster emptying of non-traditional starchy foods, which are popular among West African urban consumers.

Consumption of traditional West African pearl millet (Pennisetum glaucum) couscous delayed gastric emptying in our recent human study compared to other starch-based foods (white rice, boiled potatoes, pasta). The objective of this study was to determine whether physical properties of pearl millet couscous affect particle breakdown and starch hydrolysis during simulated gastric digestion to understand the basis of the slow gastric emptying. Starch fine structure and viscosity were analyzed for initial millet and wheat couscous samples by high performance size-exclusion chromatography and the Rapid Visco Analyzer, respectively. Couscous samples were subjected to simulated gastric digestion using the Human Gastric Simulator (HGS), a dynamic model of human gastric digestion. Digesta was collected from the HGS at 30 min intervals over 180 min. Particle size and percent starch hydrolysis of couscous in the digesta were evaluated at each time point. The number of particles per gram of dry mass substantially increased over digestion time for millet couscous (p < 0.05), while changed little for the wheat couscous samples. Millet couscous showed lower starch hydrolysis per unit surface area of particles than wheat couscous (p < 0.05). Slower starch hydrolysis was associated with smaller (p < 0.05) amylose chain length for millet (839–963 DP) than for wheat (1225–1563 DP), which may enable enable a denser packing of millet starch molecules that impedes hydrolysis. We hypothesize that the slow gastric emptying rate of millet couscous observed in humans may be explained by its slow starch hydrolysis property that could activate the ileal brake system, independent of high particle breakdown rate in the stomach.

Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region–specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling–related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.