Thermoneutral environments are defined as those in a temperature zone where a determined warm-blooded animal does not have to expend extra energy on heating. This same zone is known for facilitating accumulation of adipose tissue and decreasing brown adipose tissue activity to its minimal thermogenic level. Although high-fat diets have clearly a higher impact on body composition at this temperature zone, particularly interesting is the situation where a low-fat diet causes significant increase in the whole body lipid content. Assuming that de novo lipogenesis is exacerbated at the thermoneutral zone, our study is focused on the creation a model to indirectly predict an organism’s lipid weight gain by de novo lipogenesis over several weeks, based on a calorimetry measurement for 24 hours and the knowledge of food composition. For this study, male C57Bl6 mice living at thermoneutrality were fed a low or high-fat diet during 12 weeks at thermoneutrality (30 °C). Total lipid weight of mice was quantified by magnetic resonance imaging (EchoMRI) at each second week of experiment. Mice are gently restrained and remain conscious during the measurement, which takes around 45 seconds. At week 12, indirect calorimetry was performed during 24 h (mice remained in their home cages), when respiratory gases and exchange rate were measured. An equation was developed based on the respiratory quotient (RQ) expected for the food in comparison with the measured RQ, where the shifts towards higher values were considered proportional changes in whole-body metabolism towards de novo lipogenesis. The percentage of RQ shift was assumed to be the same percentage of O2 used in the reaction, and the conversion rate of glucose to lipids could be determined based on classic stoichiometric values. MRI analysis demonstrated that fat weight gain occurred in both food groups, being higher in the high-fat group. During room calorimetry measurement, the RQ shift towards de novo lipogenesis was only seen in low-fat-fed mice, demonstrating our basic assumptions for the calculations were correct. The equation accurately indicated the lipid weight gain by de novo lipogenesis during the first 6 weeks of experiment, but failed to predict the lack of linearity from week 6 onward. The fat weight accumulated under low-fat diet seems to originate from carbohydrates and de novo lipogenesis is absent in mice fed with a high-fat diet. Our results indicate that de novo lipogenesis probably can be quantified by the combination of room calorimetry and food composition data. Deeper understanding of each part of process is necessary for a more accurate prediction to be made and an equation to be fully accepted.