Western diets rich in saturated fat are widely implicated as triggers of metabolic disease and inflammation. However, the effects of such diets independent of weight gain are less well defined. This study assessed how an isocaloric Western diet (WD) affects metabolic, inflammatory, anthropometric, and adipose tissue transcriptomic measures when body weight is held stable.
Ninety-two twins participated in a sequential dietary intervention: 6 weeks on a healthy low-fat diet followed by 6 weeks on a Western high-fat diet. The intervention was isocaloric, and participants maintained stable body weight throughout the study. The study combined clinical measures (lipids, insulin resistance, inflammatory markers, anthropometry) with transcriptomic profiling of subcutaneous abdominal adipose tissue to evaluate molecular responses to the dietary switch.
After switching from the low-fat diet to the WD, participants showed increases in total cholesterol, LDL cholesterol, and HDL cholesterol. In contrast, plasma triglycerides and free fatty acids did not change in response to the WD. Insulin resistance increased moderately and transiently after 1 week on the WD but this change was no longer apparent after 6 weeks on the WD. These findings indicate that an isocaloric increase in dietary saturated fat can alter lipid profiles and transiently affect glucose homeostasis even without weight gain.
Some inflammatory markers showed transient and moderate elevations after 1 week on the WD. The abstract notes that these inflammatory changes disappeared by the end of the 6-week WD period. Specific inflammatory analytes reported in correlation analyses included cytokines such as IL-18 and VEGF, which were associated with molecular changes in adipose tissue; however, the abstract does not list a full panel of inflammatory markers or provide quantitative values for the time course beyond the transient rise at week 1.
Transcriptomic profiling revealed extensive changes in subcutaneous abdominal adipose tissue following the dietary switch to WD. The data are described as reflecting a restructuring of this adipose depot, indicating that the tissue underwent broad gene-expression reprogramming despite stable body weight. The abstract emphasizes that these transcriptomic changes were pronounced and widespread, but it does not present specific differentially expressed genes beyond the family of olfactory receptor transcripts discussed separately.
A notable molecular finding was an increase in olfactory receptor (OR) mRNA levels in adipose tissue after the WD exposure. The rise in adipose OR transcripts correlated positively with measures of metabolic dysfunction and ectopic fat: insulin resistance, liver fat, and visceral fat. OR expression also correlated positively with certain cytokines, including IL-18 and VEGF. Conversely, OR mRNA levels were inversely correlated with adiponectin and extracellular NAMPT. These relationships link ectopic OR expression in adipose tissue with both metabolic and inflammatory markers, suggesting a potential role for ectopic chemosensory receptors in diet-induced adipose tissue remodeling and metabolic responses.
The authors conclude that an isocaloric switch from a low-fat to a Western high-fat diet triggers metabolic and transcriptomic reprogramming that is closely associated with ectopic adipose olfactory receptor responses. Key clinical findings include elevated total, LDL, and HDL cholesterol; transient increases in insulin resistance and some inflammatory markers at 1 week; and extensive adipose tissue transcriptomic changes correlated with OR expression.
The abstract does not report detailed quantitative results, full lists of differentially expressed genes, or granular methodological parameters (for example, exact diet composition, statistical effect sizes, or full inflammatory marker panels) in the text provided. Those details would need to be obtained from the full article to evaluate effect sizes, specific gene pathways, and potential mechanistic inferences beyond the reported correlations.