Obesity, arising out of modern lifestyle has attained the status of "globesity" and affecting the health of millions of people with various socio-economic consequences. Obesity, a condition caused by imbalanced energy homeostasis, manifests itself as excessive fat deposition and often associated with several morbidities, such as type 2 diabetes, hypertension, coronary heart disease, and certain types of cancers, respiratory complications and osteoarthrites 1. Microsomal stearoyl-CoA desaturase1 (SCD1) is the rate limiting enzyme involved in the biosynthesis of monounsaturated fatty acids (MUFA); palmitoleoyl and oleoyl-CoAs from their respective substrates palmitoyl and stearoyl-CoAs by Δ⁹-cis desaturation. These MUFAs are major substrates for the synthesis of various lipids such as phospholipids (PL), triglycerides (TG), cholesteryl and wax esters. The ratio of stearic (18:0) to oleic (18:1) acids has been implicated in the regulation of cell growth and differentiation through effects on membrane fluidity and signal transduction 2. Recent studies have established that SCD1 is the most highly expressed gene in human and rodent models of obesity 34. Further, it has been shown that SCD1 determines the fate of energy, whether it should go for storage or for oxidation 5. Therefore, it appears that the SCD1 activity may be one of the crucial factors that play a major role in the development of obesity and its associated disorders.

Previously, Attie et al have reported a positive correlation between the SCD1 activity, in terms of desaturation index and plasma TG levels both in humans and mice 6. Further, another study by Mar-Heyming et al, wherein dyslipidemia has been shown to be positively correlated with plasma desaturase index in patients of familial combined hyperlipidemia 7. However, so far, no study has related the fatty acid desaturation index to physical markers of obesity such as body mass and adiposity indices (BMI & AI respectively). Therefore, here, we tried to address the relationship between the fatty acid desaturation index, an indicator of SCD1 activity, to BMI and AI of genetically obese rats of Wistar NIN strains namely, WNIN/Ob and WNIN/GR-Ob (with impaired glucose tolerance). The origin, physical and certain biochemical characteristics of these rats strains are already described in our previous publications 89.

SCD1 (Δ⁹ desaturase) is the rate limiting enzyme involved in the biosynthesis of MUFA. In many species, different isoforms of this SCD exist. In mice four isoforms; SCD1, SCD2, SCD3 and SCD4, in rat two isoforms (SCD1, SCD2) and in humans, two SCD isoforms have been identified and characterized 115. SCD1^-/--deficient mice have defective hepatic TG and CE synthesis, despite the normal activities of acyl CoA: cholesterol acyltransferase (ACAT) and diacyl glycerol: acyltransferase (DGAT) (the enzymes responsible for cholesterol ester and triglyceride synthesis respectively) and the levels of palmitoleic (16:1) and oleic (18:1) acids in plasma and tissue lipid fractions are lower, whereas palmitic (16:0) and stearic (18:0) acid levels are found to be higher than their wild type controls. These observations suggest that endogenously synthesized MUFAs by SCD1 are the main substrates for the synthesis of hepatic TG and CE 12.

In agreement with the above-mentioned study, earlier, in obese rats of WNIN/Ob strain, we reported significant increase in the fatty acid desaturation index (16:1/16:0 & 18:1/18:0) (both serum and liver), and hypertriglyceridemia, which correlated well with the over-expression of hepatic SCD1mRNA and protein compared to their age and sex-matched lean rats 10. Similar observations were made even in obese rats of WNIN/GR-Ob strain 9. Hence, it has been consistently demonstrated that hepatic over-expression of SCD1 results in elevated TG levels and increased desaturation index. In the present study, the fatty acid desaturation index (both 16:1/16:0 & 18:1/18:0) of obese rats was significantly high in plasma, liver, various white adipose tissues and BAT of both WNIN/Ob and WNIN/GR-Ob strains compared to their respective lean mates, which clearly implies that the high expression SCD1 could be responsible for this phenomenon.

Further, to confirm the fact that the SCD1 over-expression leads to hypertriglyceridemia, TG levels in lipoprotein fractions (carried out by FPLC) were estimated. Plasma FPLC profile clearly showed an increase in VLDL-associated TG levels in obese rats compared to their lean counterparts of WNIN/Ob strain. Therefore, the present data unequivocally support that the over-expression of hepatic SCD1 leads to increased TG and VLDL synthesis and secretion and therefore, hypertriglyceridemia. Though, data on plasma FPLC profile on WNIN/GR-Ob strain are lacking, we do expect the similar pattern, as the obese rats of this strain also exhibit hypertriglyceridemia. Interestingly, sterculic acid, a cyclopropane fatty acid has been shown to inhibit 90% of SCD1 enzyme activity due to reduced protein levels, which concomitantly resulted in decreased palmitoleic (16:1) and oleic (18:1) acid levels in cultured differentiating 3T3L1 adipocytes 13. Therefore, collective evidence from previous studies and the data of the present study on the fatty acid desaturation index (16:1/16:0 & 18:1/18:0) of various tissues of two obese rat strains, clearly suggest the over-expression of SCD1 in obesity.

SCD1 mRNA is highly expressed in white adipose tissue (WAT), brown adipose tissue (BAT), meibomian gland, harderian and preputial glands. This enzyme also serves as a molecular marker for adipocyte differentiation. Some of the recent studies brought out the role of SCD1 as a critical metabolic control point in energy homeostasis, since the activity of this enzyme determines whether the fatty acids should be burnt for energy release or stored as triglycerides 5. Previously, Cohen et al have demonstrated the crucial role of SCD1 in the regulation energy homeostasis in ob/ob mice. Further, these authors have also shown the repressive effect of leptin on SCD1 expression and therefore, obesity and its associated metabolic changes such as hepatic steatosis in ob/ob mice. Based on these observations, the authors concluded SCD1 as a key player in energy portioning and most of the metabolic effects of leptin are possibly mediated through the suppression of this enzyme 14. These experimental data unequivocally established SCD1 as one of the potent regulators of energy homeostasis and obesity.

In obese condition, especially in humans, assessing the extent of obesity is very crucial for proper metabolic management during weight loss program. Therefore, relating the anthropometric measures of obesity such as BMI and AI with the biochemical indicators would not only help in assessing the degree of obesity but also the extent of metabolic changes with regard to hypertriglyceridemia and metabolic syndrome. In a population-based cohort study, Waresnjo et al have shown the altered serum fatty acid composition due to SCD1 (Δ⁹), Δ⁵ and Δ⁶desaturase activities and its association with the metabolic syndrome and thereby suggesting that altered serum fatty acid composition may predict the development of metabolic syndrome 15. Very recently, in subjects with familial combined hyperlipidemia (FCHL) and fatty acid desaturation index, a significant heritable trait has been correlated with dyslipidemia 7. Interestingly, in human subjects, positive correlation between the SCD1 activity and hypertriglyceridemia has been reported 6. In agreement with this, recently, we related the over-expression of hepatic SCD1, hypertriglyceridemia and desaturation index in obese rats of WNIN/Ob strain 10. In line with previous reports, in the present study, in general, both BMI and AI positively correlated with desaturation index. Further, different tissues showed the correlation at different levels either with BMI or AI and a few of them did not. However, the consistent observation of the present study is that the plasma fatty acid Δ⁹ desaturation index (both16:1/16:0 and 18:1/18:0) exhibited strong positive correlation with the BMI and AI of rats of both WNIN/Ob and WNIN/GR-Ob strains. Hence, the current data suggest that Δ⁹ desaturation index of plasma fatty acids is a sensitive biochemical parameter that correlates with BMI and AI, besides hypertriglyceridemia, dyslipidemia and metabolic syndrome.

In conclusion, plasma fatty acid Δ⁹ desaturation index; a reflection of SCD1 activity is positively correlated with the BMI and AI in the rats of both WNIN/Ob and WNIN/GR-Ob strains. Therefore, this can be used as a simple sensitive biochemical marker not only to assess the degree of obesity, hypertriglyceridemia, but also to evaluate the efficacy of certain anti-obesity agents.

The authors declare that they have no competing interests.

SMJ was responsible for animal killing, blood and tissue collection, acquisition of data, analysis and manuscript preparation. PL assisted in plasma FPLC-TG analysis. SP was responsible for fatty acid composition analysis by GC. NB was responsible for the statistical analysis. NVG provided WNIN-mutant strain rats for the study. AV was responsible for the funding, study design, data acquisition, analysis, interpretation & manuscript preparation. All authors read and approved the final manuscript.