Ability of GLP-1 to decrease food intake is dependent on nutritional status

UnlabelledGut-derived glucagon like peptide-1 (GLP-1) acts in the postprandial period to stimulate insulin secretion and inhibit gastrointestinal motor and secretory function; whether endogenous peripheral GLP-1 inhibits food intake is less clear. We hypothesized that GLP-1 inhibits food intake in the fed, but not fasted, state. There is evidence that GLP-1 acts via stimulation of vagal afferent neurons (VAN); we further hypothesized that the satiating effects of endogenous GLP-1 in the postprandial period is determined either by a change in GLP-1 receptor (GLP-1R) expression or localization to different cellular compartments in VAN.MethodsFood intake was recorded following administration of GLP-1 (50μg/kg or 100μg/kg) or saline (IP) in Wistar rats fasted for 18h or fasted then re-fed with 3g chow. GLP-1R protein expression and localization on VAN were determined by immunocytochemistry and immunoblots in animals fasted for 18h or fasted then re-fed for 40min. GLP-1R mRNA level was detected in animals fasted for 18h or fasted and re-fed ad libitum for 2h.ResultsGLP-1 (100μg/kg) significantly reduced 40min food intake by 38% in re-fed but not fasted rats (p<0.05). GLP-1R mRNA or protein levels in VAN were unchanged in re-fed compared to fasted rats. However, GLP-1R localization to the plasma membrane was significantly increased in VAN by feeding.ConclusionFeeding changes the ability of peripheral GLP-1 to inhibit food intake. GLP-1Rs are trafficked to the plasma membrane in response to a meal. GLP-1 may play a role in regulating food intake in the postprandial period

Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats

International audiencePurpose - Reduced ability of cholecystokinin (CCK) to induce satiation contributes to hyperphagia and weight gain in high-fat/high-sucrose (HF/HS) diet-induced obesity, and has been linked to altered gut microbiota. Rodent models of obesity use chow or low-fat (LF) diets as control diets; the latter has been shown to alter gut microbiota and metabolome. We aimed to determine whether LF-diet consumption impacts CCK satiation in rats and if so, whether this is prevented by addition of inulin to LF diet. Methods - Rats (n = 40) were fed, for 8 weeks, a chow diet (chow) or low-fat (10%) or high-fat/high-sucrose (45 and 17%, respectively) refined diets with either 10% cellulose (LF and HF/HS) or 10% inulin (LF-I and HF/HS-I). Caecal metabolome was assessed by H-NMR-based metabolomics. CCK satiation was evaluated by measuring the suppression of food intake after intraperitoneal CCK injection (1 or 3 µg/kg). Results - LF-diet consumption altered the caecal metabolome, reduced caecal weight, and increased IAP activity, compared to chow. CCK-induced inhibition of food intake was abolished in LF diet-fed rats compared to chow-fed rats, while HF/HS diet-fed rats responded only to the highest CCK dose. Inulin substitution ameliorated caecal atrophy, reduced IAP activity, and modulated caecal metabolome, but did not improve CCK-induced satiety in either LF- or HF/HS-fed rats. Conclusions - CCK signaling is impaired by LF-diet consumption, highlighting that caution must be taken when using LF diet until a more suitable refined control diet is identified

Sex differences in response to short-term high fat diet in mice

BackgroundConsumption of high-fat diet (HF) leads to hyperphagia and increased body weight in male rodents. Female rodents are relatively resistant to hyperphagia and weight gain in response to HF, in part via effects of estrogen that suppresses food intake and increases energy expenditure. However, sex differences in energy expenditure and activity levels with HF challenge have not been systemically described. We hypothesized that, in response to short-term HF feeding, female mice will have a higher energy expenditure and be more resistant to HF-induced hyperphagia than male mice.MethodsSix-week-old male and female C57BL/6 J mice were fed either low fat (LF, 10% fat) or moderate HF (45% fat) for 5 weeks, and energy expenditure, activity and meal pattern measured using comprehensive laboratory animal monitoring system (CLAMS).ResultsAfter 5 weeks, HF-fed male mice had a significant increase in body weight and fat mass, compared with LF-fed male mice. HF-fed female had a significant increase in body weight compared with LF-fed female mice, but there was no significant difference in fat mass. HF-fed male mice had lower energy expenditure compared to HF-fed female mice, likely due in part to reduced physical activity in the light phase. HF-fed male mice also had increased energy intake in the dark phase compared to LF-fed male mice and a reduced response to exogenous cholecystokinin-induced inhibition of food intake. In contrast, there was no difference in energy intake between LF-fed and HF-fed female mice.ConclusionsThe data show that female mice are generally protected from short-term HF-induced alterations in energy balance, possibly by maintaining higher energy expenditure and an absence of hyperphagia. However, HF-feeding in male mice induced weight and fat mass gain and hyperphagia. These findings suggest that there is a sex difference in the response to short-term HF-feeding in terms of both energy expenditure and control of food intake

Ability of GLP-1 to decrease food intake is dependent on nutritional status

Gut-derived glucagon like peptide-1 (GLP-1) acts in the postprandial period to stimulate insulin secretion and inhibit gastrointestinal motor and secretory function; whether endogenous peripheral GLP-1 inhibits food intake is less clear. We hypothesized that GLP-1 inhibits food intake in the fed, but not fasted, state. There is evidence that GLP-1 acts via stimulation of vagal afferent neurons (VAN); we further hypothesized that the satiating effects of endogenous GLP-1 in the postprandial period is determined either by a change in GLP-1 receptor (GLP-1R) expression or localization to different cellular compartments in VAN. METHODS: Food intake was recorded following administration of GLP-1 (50 μg/kg or 100μg/kg) or saline (IP) in Wistar rats fasted for 18h or fasted then re-fed with 3g chow. GLP-1R protein expression and localization on VAN was determined by immunocytochemistry and immunoblots in animals fasted for 18h or fasted then re-fed for 40mins. GLP-1R mRNA level was detected in animals fasted for 18h or fasted and re-fed ad libitum for 2h. RESULTS: GLP-1 (100μg/kg) significantly reduced 40 min food intake by 38% in re-fed but not fasted rats (p<0.05). GLP-1R mRNA or protein levels in VAN were unchanged in re-fed compared to fasted rats. However, GLP-1R localization to the plasma membrane was significantly increased in VAN by feeding. CONCLUSION: Feeding changes the ability of peripheral GLP-1 to inhibit food intake. GLP-1Rs are trafficked to the plasma membrane in response to a meal. GLP-1 may play a role in regulating food intake in the postprandial period