Learning how to lose weight with MTHFR starts with understanding the connection between MTHFR, SAMe, and the PEMT gene. The PEMT gene requires up to 70% of SAMe to make phosphatidylcholine which is crucial for liver detoxification and weight loss. Reversing fatty liver is essential for weight loss, and SNPs in the MTHFR gene or PEMT gene can make weight loss difficult due to a fatty liver.