scholarly journals Decoy bypass for appetite suppression in obese adults: role of synergistic nutrient sensing receptors GPR84 and FFAR4 on colonic endocrine cells

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323219
Author(s):  
Madusha Peiris ◽  
Rubina Aktar ◽  
David Reed ◽  
Vincent Cibert-Goton ◽  
Ausra Zdanaviciene ◽  
...  
Keyword(s):  
Energy Intake ◽  
Metabolic Regulation ◽  
Endocrine Cells ◽  
Sensory Nerve ◽  
Serotonin Release ◽  
Nutrient Sensing ◽  
Colonic Delivery ◽  
Obese Adults ◽  
Double Blind ◽  
Synergistic Activation

ObjectiveColonic enteroendocrine cells (EECs) store and release potent anorectic hormones that are key regulators of satiety. EECs express multiple nutrient sensing receptors, particularly for medium-chain fatty acids (MCFAs): GPR84 and FFAR4. Here we show a non-surgical approach with targeted colonic delivery of MCFA, which induces EEC and neuronal activation leading to anorectic effects.DesignA randomised, double-blind, placebo-controlled, cross-over study was performed in obese adults given combined GPR84 and FFAR4 agonists in colonic release capsules before meals. We measured serum hormones, energy intake and appetite perception. Cell type, activation by agonists and hormone/serotonin release were determined in human colonic explants. Mouse colonic afferent nerve responses to nutrients/mediators were recorded electrophysiologically.ResultsSubjects receiving GPR84 and FFAR4 agonists had reduced overall calorific intake and increased postprandial levels of PYY versus placebo. Receptors including GPR84 and FFAR4 were coexpressed on human colonic EEC. Activation of GPR84 exclusively induced intracellular pERK, whereas FFAR4 selectively activated pCaMKII. Coactivation of GPR84 and FFAR4 induced both phosphoproteins, and superadditive release of GLP-1 and PYY. Nutrients and hormones convergently activated murine colonic afterent nerves via GLP-1, Y2 and 5-HT3 receptors.ConclusionsColonic GPR84 and FFAR4 agonists reduce energy intake and increase postprandial PYY in obese adults. Human colonic EECs coexpress these receptors, which activate cells via parallel intracellular pathways and synergistically evoke hormone release. Further synergism occurs in sensory nerve responses to MCFA and EEC mediators. Thus, synergistic activation of colonic endocrine cells via nutrient receptors is an important target for metabolic regulation.Trail registration numberNCT04292236.

scholarly journals Changes in Weight and Substrate Oxidation in Overweight Adults Following Isomaltulose Intake During a 12-Week Weight Loss Intervention: A Randomized, Double-Blind, Controlled Trial

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2367 ◽  
Author(s):  
Lightowler ◽  
Schweitzer ◽  
Theis ◽  
Henry
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Energy Intake ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Body Weight Loss ◽  
Fat Oxidation ◽  
Obese Adults ◽  
Double Blind ◽  
Body Weight Reduction

Low-glycemic compared to high-glycemic diets have been shown to improve metabolic status and enhance fat oxidation. The randomized, double-blind, controlled intervention study aimed to evaluate the effects of an energy-reduced diet containing isomaltulose (ISO, Palatinose™) versus sucrose (SUC) on body weight loss. Sixty-four healthy overweight/obese adults were allocated to consume either 40g/d ISO or SUC added to an energy-reduced diet for 12 weeks. Anthropometric measurements, body composition, and energy metabolism were assessed at baseline and after 4, 8, and 12 weeks. Fifty participants (age: 40.7 ± 11.7 y; BMI: 29.4 ± 2.7 kg/m²) completed the study. During the 12 weeks, both groups significantly lost weight (p < 0.001), which was more pronounced following ISO (−3.2 ± 2.9 vs. −2.1 ± 2.6 kg; p = 0.258). Moreover, for participants in the ISO group, this was accompanied by a significant reduction in fat mass (ISO: −1.9 ± 2.5, p = 0.005; SUC: −0.9 ± 2.6%, p = 0.224). The overall decrease in energy intake was significantly higher in the ISO compared to that in the SUC group (p = 0.022). In addition, breakfast containing ISO induced a significantly lower increase in postprandial respiratory quotient (RQ) (mean incremental area under the curve (iAUC)2h for ISO vs. SUC: 4.8 ± 4.1 vs. 6.9 ± 3.1, p = 0.047). The results suggest that ISO in exchange for SUC may help to facilitate body weight reduction, lower postprandial RQ associated with higher fat oxidation, and reduce energy intake.

The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling

2014 ◽  
Vol 306 (6) ◽  
pp. E581-E591 ◽  
Author(s):  
Yun Chau Long ◽  
Theresa May Chin Tan ◽  
Inoue Takao ◽  
Bor Luen Tang
Keyword(s):  
Cell Biology ◽  
Metabolic Regulation ◽  
Nutrient Sensing ◽  
Cellular Aging ◽  
Retrograde Signaling ◽  
Unfolded Protein ◽  
Mitochondrial Retrograde Signaling ◽  
Long Time ◽  
Biology Of Aging ◽  
Protein Response

Cellular and organ metabolism affects organismal lifespan. Aging is characterized by increased risks for metabolic disorders, with age-associated degenerative diseases exhibiting varying degrees of mitochondrial dysfunction. The traditional view of the role of mitochondria generated reactive oxygen species (ROS) in cellular aging, assumed to be causative and simply detrimental for a long time now, is in need of reassessment. While there is little doubt that high levels of ROS are detrimental, mounting evidence points toward a lifespan extension effect exerted by mild to moderate ROS elevation. Dietary caloric restriction, inhibition of insulin-like growth factor-I signaling, and inhibition of the nutrient-sensing mechanistic target of rapamycin are robust longevity-promoting interventions. All of these appear to elicit mitochondrial retrograde signaling processes (defined as signaling from the mitochondria to the rest of the cell, for example, the mitochondrial unfolded protein response, or UPRmt). The effects of mitochondrial retrograde signaling may even spread to other cells/tissues in a noncell autonomous manner by yet unidentified signaling mediators. Multiple recent publications support the notion that an evolutionarily conserved, mitochondria-initiated signaling is central to the genetic and epigenetic regulation of cellular aging and organismal lifespan.

scholarly journals Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity

2019 ◽  
Vol 316 (3) ◽  
pp. G332-G337 ◽  
Author(s):  
Carsten Dirksen ◽  
Jesper Graff ◽  
Stefan Fuglsang ◽  
Jens F. Rehfeld ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Olive Oil ◽  
Energy Intake ◽  
Severe Obesity ◽  
Gastrointestinal Transit ◽  
Calorie Intake ◽  
Double Blind ◽  
Gut Hormone ◽  
Ad Libitum

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2(range of 47.9–69.0)] and 10 men without obesity [BMI of 24.6 kg/m2(range of 21.7–26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipidP = 0.046; GMETwaterP = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion.NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.

scholarly journals Eight-day consumption of inulin added to a yogurt breakfast lowers postprandial appetite ratings but not energy intakes in young healthy females: a randomised controlled trial

2015 ◽  
Vol 115 (2) ◽  
pp. 262-270 ◽  
Author(s):  
Sarah Heap ◽  
Jessica Ingram ◽  
Marron Law ◽  
Amy J. Tucker ◽  
Amanda J. Wright
Keyword(s):  
Energy Intake ◽  
Controlled Trial ◽  
Eating Behaviour ◽  
Hormonal Contraceptives ◽  
Double Blind ◽  
Randomised Controlled ◽  
Desire To Eat ◽  
Repeated Consumption ◽  
Healthy Females

AbstractIncreasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.

scholarly journals Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial

Metabolism ◽  
2018 ◽  
Vol 85 ◽  
pp. 116-125 ◽  
Author(s):  
Alessio Basolo ◽  
Joshua Burkholder ◽  
Kristy Osgood ◽  
Alexis Graham ◽  
Sarah Bundrick ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Energy Intake ◽  
Controlled Trial ◽  
Pronounced Effect ◽  
Double Blind ◽  
Double Blind Placebo
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