PMC

(A) Body weight of three-month-old Ffar3 knockouts and wild-type littermates on standard chow diet and one week after switching to HFD. N=34–41. (B-D) After one week of HFD feeding, Ffar3 knockouts and wild-type littermates were switched to HFD containing sodium butyrate (5%) or sodium propionate (4.3%) for eight days. Cumulative body weight change and daily food intake are shown. Data are mean ± SEM. N=8–13. *P<0.05, **P<0.01, ***P<0.001 vs. control diet. #P<0.05 vs. wild-type mice on control diet. NS: not significant.

(A-C) Three-month-old lean C57BL/6N mice were switched to HFD containing sodium salts of butyrate (5%), propionate (4.3%), and acetate (3.7%) for nine days. Daily food intake, cumulative food intake, and cumulative locomotor activity are shown. L: light phase. D: dark phase. (D, E) Dose titration of sodium butyrate and sodium propionate in HFD was performed in three-month-old lean C57BL/6N mice. Eight-day cumulative body weight change and food intake are shown. Data are mean ± SEM. N=8. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs. control diet.

(A-F) Three-month-old lean C57BL/6N mice were fasted overnight and orally dosed with saline, sodium butyrate, sodium propionate, sodium acetate, an SCFA admixture (65% sodium acetate, 20% sodium propionate, 15% sodium butyrate), octanoic acid (OA), or α-linolenic acid (LA), all at 400mg/kg body weight. Plasma levels of total GLP-1, active GLP-1, GIP, PYY, insulin, and amylin were measured 10 minutes after dosing. Intra-assay CV% was below 8.9% for all immunoassays. Data are mean ± SEM. N=8. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs. saline. NS: not significant.

(A) Ffar3 mRNA expression determined by quantitative RT-PCR in the mucosal and smooth muscle (SM) layers of different intestinal segments from lean C57BL/6N mice and in GLUTag cells. Data are normalized against Rplp0 mRNA. N=3. (B-H) After four weeks of HFD feeding, five-month-old Ffar3 knockout mice and wild-type littermates were fasted overnight and dosed with saline, sodium butyrate, or sodium propionate (400mg/kg). Plasma levels of total GLP-1, active GLP-1, GIP, PYY, insulin, and ghrelin were measured 10 minutes after dosing. Intra-assay CV% was below 7.6% for all immunoassays. N=8. Data are mean ± SEM. *P<0.05, **P<0.01, ***P<0.001, NS: not significant.

(A) Body composition was determined by quantitative NMR in Ffar3 knockouts and wild-type littermates after five months of HFD feeding. (B, C) Plasma leptin levels were determined in overnight fasted Ffar3 knockouts and wild-type littermates maintained on standard chow diet or HFD. (D) Blood glucose was measured in ad libitum fed mice maintained on HFD three hours after the start of the light phase. (E) Oral glucose tolerance test after overnight fasting and (F) intraperitoneal insulin tolerance test after five-hour daytime fasting in Ffar3 knockouts and wild-type littermates maintained on HFD. Data are mean ± SEM. N=8–14.

Three-month-old lean C57BL/6N mice were switched to HFD containing molarity-matched sodium salts of butyrate (5% w/w), propionate (4.3%), and acetate (3.7%) for four weeks. (A) Body weight was measured weekly, and four-week cumulative weight gain is expressed as a percentage of initial body weight. (B) Oral glucose tolerance test was performed in overnight fasted mice four weeks after diet switch. Blood glucose levels and total glucose area-under-the-curve (AUC) are shown. (C, D) Plasma levels of insulin and leptin were determined in overnight fasted mice four weeks after diet switch. Data are mean ± SEM. N=8. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 vs. control HFD.