4. Discussion
obesity, T2D, fat loss, hypoglycemia, caloric deficit
OBESITY, HYPOGLYCEMIA, CVD
The main observation of this work is, short-term caloric restriction with or without exercise decreased fasting LEAP-2 in women with obesity. However, when examining the impact of glucose ingestion on LEAP-2, it was observed that LCD raised LEAP-2 more than LCD+INT. The observed reductions in fasting LEAP-2 and rise in glucose-stimulated LEAP-2 after LCD, but not LCD+INT, is contrary to our hypothesis that exercise would raise LEAP-2 during an LCD. We anticipated such a blunted decline and rise in LEAP-2 given the literature suggests exercise may reduce appetite, as well as improve glucose regulation. Consistent with prior literature though, our work confirms that of Holm et al. [There are potential explanations for why LEAP-2 was altered post-treatment. Reductions in body weight and/or fat have been linked to lower LEAP-2 [We also recognize that the reduced carbohydrate oxidation during the OGTT in LCD post-treatment from our prior work may hint at glycogen storage vs. oxidation being a factor regulating LEAP-2 during the post-prandial period. Indeed, during energy deficit LEAP-2 has been reported to decline in effort to raise blood glucose for the prevention of hypoglycemia via a potential influence of glucagon mediated hepatic glucose production [LEAP-2 has gained interest as a potential pharmaceutical drug given exogenous administration suppresses hunger and decreases food intake [It is important to consider limitations in the current work. The energy deficit of the current investigation was over the course of 2 weeks and the results may change with a longer caloric deficit. LCD lost more body fat than LCD+INT and this could impact our outcomes. Why LCD lost slightly more weight/fat is beyond the scope of this analysis but could be due to either estimating energy expenditure from exercise and refeeding an absolute amount of calories post-exercise or changes in sedentary behavior. Either way, we covaried for fat loss, and this did not impact LEAP-2. This confirms that, despite both groups losing weight, and LCD inducing approximately 0.8 kg more fat loss than LCD+INT, there was no influence on LEAP-2. Testing was performed within 24 h from the last exercise session, and LEAP-2 kinetics during the immediate to longer post-exercise period (e.g., 3 to 72 h) is unknown. LEAP-2 were collected at 0, 30, and 60 min of the OGTT and it is possible we missed the exact effect of circulating and changes in LEAP-2 on the VAS measurement. However, insulin, ghrelin, GLP-1 and other appetite hormones often peak or nadir in this same time period [In conclusion, 2 weeks of a LCD, with and without interval training lowered fasting LEAP-2. However, LCD raised glucose-stimulated LEAP-2 compared with LCD+INT. This suggests diet and exercise may influence post-prandial LEAP-2, while energy deficit is an important regulator of fasting LEAP-2. In either case, lower LEAP-2 was related to reduced desires for sweet and salty foods post-intervention only. Together, these observations suggest LEAP-2 may play a role in calorically dense food choices and glucose regulation. Thus, future work is needed to understand how LEAP-2 may impact food intake and plasma glucose following lifestyle therapy to prevent/treat obesity, T2D, and CVD. 