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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 Ca 2+ 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. Food intake is determined by learned appetitive responses and physiological “appetition” signals after eating begins. Here, authors show melanin-concentrating hormone (MCH)-producing neurons integrate these processes to promote caloric intake.

Children frequently consume beverages that are either sweetened with sugars (sugar-sweetened beverages; SSB) or low-calorie sweeteners (LCS). Here, we evaluated the effects of habitual early life consumption of either SSB or LCS on energy balance later during adulthood. Male and female rats were provided with chow, water, and a solution containing either SSB (sucrose), LCS (acesulfame potassium (ACE-K) or stevia), or control (no solution) during the juvenile and adolescent periods (postnatal days 26–70). SSB or LCS consumption was voluntary and restricted within the recommended federal daily limits. When subsequently maintained on a cafeteria-style junk food diet (CAF; various high-fat, high-sugar foods) during adulthood, ACE-K-exposed rats demonstrated reduced caloric consumption vs. the controls, which contributed to lower body weights in female, but not male, ACE-K rats. These discrepant intakes and body weight effects in male ACE-K rats are likely to be based on reduced gene expression of thermogenic indicators (UCP1, BMP8B) in brown adipose tissue. Female stevia-exposed rats did not differ from the controls in terms of caloric intake or body weight, yet they consumed more SSB during CAF exposure in adulthood. None of the SSB-exposed rats, neither male nor female, differed from the controls in terms of total adult caloric consumption or body weight measures. The collective results reveal that early life LCS consumption alters sugar preference, body weight, and gene expression for markers of thermogenesis during adulthood, with both sex- and sweetener-dependent effects.

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.

In a previous trial in Mali, we showed that traditional pearl millet couscous and thick porridge delayed gastric emptying (about 5 h half-emptying times) in a normal-weight population compared with non-traditional carbohydrate-based foods (pasta, potatoes, white rice; about 3 h half-emptying times), and in a gastric simulator we showed millet couscous had slower digestion than wheat couscous. In light of these findings, we tested the hypothesis in a normal-weight US population (n 14) that millet foods would reduce glycaemic response (continuous glucose monitor), improve appetitive sensations (visual analogue scale ratings), as well as reduce gastric emptying rate (13C-octanoic acid breath test). Five carbohydrate-based foods (millet couscous – commercial and self-made, millet thick porridge, wheat couscous, white rice) were fed in a crossover trial matched on available carbohydrate basis. Significantly lower overall glycaemic response was observed for all millet-based foods and wheat couscous compared with white rice (P ≤ 0·05). Millet couscous (self-made) had significantly higher glycaemic response than millet couscous (commercial) and wheat couscous (P < 0·0001), but as there were no differences in peak glucose values an extended glycaemic response was indicated for self-made couscous. Millet couscous (self-made) had significantly lower hunger ratings and higher fullness ratings (P < 0·05) than white rice, millet thick porridge and millet couscous (commercial). A normal gastric emptying rate (<3 h half-emptying times) was observed for all foods, with no significant differences among them. In conclusion, some traditionally prepared pearl millet foods show the potential to reduce glycaemic response and promote satiety.

Purpose Superior metabolic flexibility, or the ability to efficiently switch between oxidation of carbohydrate and fat, is inversely associated with obesity and type 2 diabetes. The influence of dietary factors on metabolic flexibility is incompletely understood. This study examined the impact of dietary carbohydrate digestion rate on metabolic flexibility and metabolic substrate utilization. Methods We employed percent relative cumulative frequency (PRCF) analyses coupled with a new application of modeling using the Mixed Weibull Cumulative Distribution function to examine respiratory exchange ratio (RER) data from adult wild-type mice and mice lacking the mucosal maltase-glucoamylase enzyme (Mgam) under different dietary carbohydrate conditions, with diets matched for total carbohydrate contents and containing different ratios of slowly digestible starch (SDS) and resistant starch (RS), or that were high in sucrose or fat. Fungal amyloglucosidase (AMG) was administered in drinking water to increase carbohydrate digestion rate. We devised a Metabolic Flexibility Factor (MFF) to quantitate metabolic flexibility for each dietary condition and mouse genotype, with higher MFF indicating higher metabolic flexibility. Results Diets high in SDS exhibited lower average RER and higher metabolic flexibility (MFF) than diets high in resistant starch, sucrose, or fat. Diets containing high and intermediate amounts of SDS led to a more complete shift to fat oxidation. While mouse genotype had minimal effects on substrate oxidation and MFF, AMG supplementation shifted substrate utilization to carbohydrate oxidation and generally decreased MFF. Conclusions Consumption of slowly digestible carbohydrates improved measures of metabolic substrate utilization at the whole-body level in adult mice.

PurposeTo test the hypothesis that oral ingestion of slowly digestible carbohydrates (SDCs) that reach the ileum triggers the ileal brake as indicated by delayed gastric emptying, reduced glycemic response, and decreased subjective appetite.MethodsThe study was a five-arm, randomized, double-blind, crossover trial with a 1-week washout period between treatments (n = 20; 9 females, 11 males). Five treatments consisted of three SDC ingredients [raw corn starch, isomaltooligosaccharide (IMO), sucromalt], and an IMO/sucromalt combination, shown in vitro to have slow and extended digestion profiles, and a rapidly digestible carbohydrate control (maltodextrin). Carbohydrates (26 g) were incorporated into yogurt [300 g total; carbohydrate (~ 77 g), fat (~ 0.2 g), and protein (~ 9 g)] with closely matched energy content (346 kcal) and viscosity (~ 30,000 cP). Outcomes were measured in a 4 h postprandial period.ResultsMean gastric half-emptying times were moderately though significantly increased for the raw corn starch and IMO treatments (P < 0.05), but they could be sub-divided into larger effect responder (n = 11) and non-responder groups (n = 9). Longer time for glycemic response to return to baseline was associated with increased gastric half-emptying time in an exploratory subset of data removing gastric half-emptying times > 3.5 h (P = 0.02). No significant differences in appetite ratings were observed.ConclusionSDCs caused slower gastric emptying rate through activation of the ileal brake, as closely matched semi-solid yogurts were used and only rate of carbohydrate digestion differed. Extending glycemic response through consumption of SDCs was associated with triggering the ileal brake.Trial registrationClinicalTrials.gov NCT03630445, August 2018, retrospectively registered.

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.

Approximately 14% of U.S. households are estimated to be food insecure. The neurocognitive and metabolic impacts of unpredictable food access during early-life periods of development are poorly understood. To address these gaps we devised a novel rat model of food insecurity to control the timing, type, and quantity of accessible food using programmable feeders. Male rats were divided into 3 groups: Secure-chow (SC), a control group given 100% of daily caloric needs, distributed evenly across 4 daily meals of standard chow at set mealtimes; Secure-mixed (SM), a 2nd control group identical to the SC group except that the food type predictably alternated daily between chow and a high-fat, high-sugar diet (HFHS); and Insecure-mixed (IM), the experimental group given randomly alternating daily access to either chow or HFHS at either 85% or 115% of daily caloric needs, distributed evenly across 3 daily meals with unpredictable mealtimes. These feeding schedules were implemented from postnatal days (PNs) 26-45, after which all groups received chow ad libitum. Metabolic assessments performed in adulthood revealed no group differences in caloric intake, body weight, or body composition when maintained on either chow (PN46-149) or a cafeteria diet (PN150-174). Behavioral measures (PN66-126) revealed no group differences in anxiety-like, exploratory, or impulsive behavior (zero maze, open field, differential reinforcement of low rates of responding procedures). However, the IM group exhibited hippocampus-dependent memory impairments compared to both control groups in the novel location recognition test. These findings suggest that early-life food insecurity may contribute to long-term impairments in memory function.

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26-41; WD-EA) or late-adolescent period (PN 41-56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.