Peroxisome proliferator-activated receptor gamma (PPARγ) responds to thiazolidinedione derivatives, which are ligands of PPARγ, and affects insulin resistance. Recently, a PPARγ study reported that in high-fat-diet-induced obesity, the phosphorylation of PPARγ prevented the transcription of specific PPARγ targets that have anti-obesity effects. We previously reported that genetic variants of the fatty acid desaturase were associated with plasma lipid profiles and could contribute to dyslipidemia in Japanese males. The aim of this study was to investigate the anti-obesity effects of PPARγ variants on lipid profiles. One hundred and thirty-eight (138) Japanese males participated in the study. Their serum lipid markers and the fatty acid composition of their red blood cell (RBC) membranes were determined. The stearoyl-CoA desaturase 1 (SCD1) indices were represented as the fatty acid product : precursor ratios. The participants were genotyped for the single-nucleotide polymorphism rs2938392 in the PPARγ gene. The participants' fitness habits were also surveyed by questionnaire. The effects of habitual exercise on the measured lipid parameters were compared in each genotype group. No association between the genotypes in the PPARγ gene and the biochemical data was found. However, the serum triglyceride levels and the SCD1 indices in RBC membranes were significantly higher in the participants who carried the major rs2938392 allele (A/A) and did not habitually exercise than in those who did exercise. These findings indicate that the risk for detrimental lipid profiles in the absence of habitual exercise depends on the PPARγ genotype in Japanese males.