Progesterone Treatment Attenuates Body Weight Gain, Adiposity and Glycaemic Metabolism Damage in Obese Female Mice

Abstract

Since the incidence of gestational diabetes is higher in obese women and those treated with progestogens during pregnancy, the aim of this study was to investigate the effect of progesterone (PG) on body composition, glucose metabolism and metabolic parameters in obese female mice. Post‐weaned female C57Bl/J6 were distributed into four groups: normocaloric control (NO‐CO, n=11), high fat and fructose control (HFF‐CO, n=10), normocaloric PG (NO‐PG, n=8) and high fat and fructose PG (HFF‐PG, n=9). The NO‐CO and NO‐PG mice fed a AING93 standard diet and the HFF‐CO and HFF‐PG fed a AIN93G diet added of lard (31%) and fructose (24%) during 10 weeks. In the 7th week, NO‐PG and HFF‐PG received an osmotic pump implant for constant infusion (0,25 mg/kg/d) of PG. All procedures were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (003/2018). The daily food intake in grams was similar in all groups, but in terms of calories, the intake of the HFF‐CO and HFF‐PG (13.24+0.9 and 13.06+0.72 kcal/animal) groups was higher than NO‐CO and NO‐PG (9.22+0.2 and 9.53+0.53 kcal/animal) groups. The body weight gain was greater the HFF‐CO and HFF‐PG (11.52+0.94 and 9.61+0.85 g) groups compared to NO‐CO and NO‐PG (5.85+0.51 and 5.69+0.5 g) groups. Considering the final body weight of these animals (NO‐CO, 22.14+0.34 g; NO‐PG, 21.89+0.33 g; HFF‐CO, 28.76+0.59 g; HFF‐PG, 26.27+0.67 g) we observed not only the predicted increase in the weight of groups that received the HFF‐CO diet but also a lower increase in HFF‐PG group compared to HFF‐CO group. White adipose tissue fat pads (subcutaneous, SC‐WAT and retroperitoneal, RP‐WAT) increased significantly in the HFF‐CO group compared to NO‐CO and PG groups. In HFF‐PG, both WAT fat pads were greater compared to NO‐PG group, but only the WAT‐RP was greater compared to NO‐CO group. No differences were observed in interscapular brown adipose tissue and pancreas weight. On the other hand, the weight of liver was lower in HFF and HFF‐PG compared to NO‐CO and PG groups. No difference was found in the fasting glycaemia in the animals. From the results of the GTT and area under the curve (AUC) we observed that the HFF (23907+1304 mg/dL/120min) presented significantly higher AUC than NO‐CO and NO‐PG (17327+1042 and 18096+989 mg/dL/120min) groups. In addition, kITT of HFF‐CO (2.86+0.26 %/min) was significantly smaller compared to NO‐CO (4.23+0.56 %/min), NO‐PG (4.07+0.64 %/min) and HFF‐PG (3.89+0.4 %/min). Metabolic parameters measured in the indirect calorimetry during resting such as resting oxygen consumption, energy expenditure, respiratory exchange ratio, and the rates of carbohydrate and lipids oxidation did not differ among groups. In conclusion, the treatment with PG in a concentration that mimics those found in pregnancy attenuated body weight gain, adiposity and glycaemic metabolism damage observed in obese female mice.