Feline lipid metabolism is a topic for greater exploration due to this specie?s unique characteristics. Cats express limited Delta 6-desaturase activity necessary for conversion of linoleic acid (LA, 18:2n-6) to arachidonic acid (AA, 20:4n-6). The possibility exists that Gamma-linolenic acid (GLA, 18:3n-6) may serve as a precursor of AA in reproductive tissues especially if coupled with chain elongation and a functionally active Delta 5-desaturase. In addition no research has been conducted regarding feline reproductive Delta 8-desaturase activity as an alternate to the production of AA. To investigate desaturation activities, a group of 26 adult female cats were randomly assigned into 1 of 3 groups based on the diet fed: High Linoleic Acid (HL, n=7), Low Linoleic Acid (LL, n=9), and High Gamma-Linolenic Acid (GLA, n=10).The diets were fed for 300 days prior to ovariohysterectomy at which time EDTA plasma and ovarian, uterine, and subcutaneous adipose tissues were collected. Homogenates of each tissue were prepared and frozen in aliquots at -80 degrees C. Total lipids were extracted from the plasma and tissue homogenates followed by phospholipid (PL) fractionation via thin layer chromatography and fatty acid (FA) analyses by gas chromatography. The Shapiro-Wilks test was used to determine normal distribution of FA data followed by One-Way ANOVA and Tukey multiple comparisons (p<0.05). Plasma PLs were significantly increased in both GLA and dihomo-Gamma-linolenic acid (DGLA, 20:3n-6Delta8,11,14) in the GLA group and statistically increased in 20:2n-6 and 20:3n-6(Delta5,11,14) in the HL group. Uterine tissue homogenates had significantly increased amounts of DGLA and AA, however ovarian tissue showed an increase of only DGLA. Adipose tissue FAs showed significantly high amounts of DGLA in the GLA group. It is concluded that a high GLA diet results in increased AA in uterine, but not ovarian, tissues and thus may supply eicosanoid precursors in support of reproduction. The presence of increased amounts of 20:3n-6(Delta5,11,14) and not AA in the plasma and uterine tissues in the HL group suggests that Delta6-desaturase cannot be induced and that Delta8-desaturase is not active when feeding high dietary LA. Furthermore, the increase in DGLA may provide an adipose storage reservoir for additional conversion under times of metabolic need. These data support the presence of a functionally active Delta5-desaturase in uterine, but not ovarian, tissues. The findings also suggest that increased dietary GLA may be used to meet the AA requirements for reproduction in cats in the absence of an animal based pre-formed source of AA.

<p>The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.</p><p>In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.</p><p>This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.</p>

The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios. In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice. This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

The gastrointestinal tract (GIT) regulates nutrient uptake, secretes hormones and has a crucial gut flora and enteric nervous system. Of relevance for these functions are the G protein-coupled receptors (GPCRs) and the solute carriers (SLCs). The Adhesion GPCR subfamily is known to mediate neural development and immune system functioning, whereas SLCs transport e.g. amino acids, fatty acids (FAs) and drugs over membranes. We aimed to comprehensively characterize Adhesion GPCR and SLC gene expression along the rat GIT. Using qPCR we measured expression of 78 SLCs as well as all 30 Adhesion GPCRs in a twelve-segment GIT model. 21 of the Adhesion GPCRs had a widespread (≥5 segments) or ubiquitous (≥11 segments) expression. Restricted expression patterns were characteristic for most group VII members. Of the SLCs, we found the majority (56 %) of these transcripts to be expressed in all GIT segments. SLCs were predominantly found in the absorption-responsible gut regions. Both Adhesion GPCRs and SLCs were widely expressed in the rat GIT, suggesting important roles. The distribution of Adhesion GPCRs defines them as a potential pharmacological target. FAs constitute an important energy source and have been implicated in the worldwide obesity increase. FAs and their ratios – indices for activities of e.g. the desaturase enzymes SCD-1 (SCD-16, 16:1n-7/16:0), D6D (18:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) – have been associated with e.g. overall mortality and BMI. We examined whether differences in FAs and their indices in five lipid fractions contributed to obesity susceptibility in rats fed a high fat diet (HFD), and the associations of desaturase indices between lipid fractions in animals on different diets. We found that on a HFD, obesity-prone (OP) rats had a higher SCD-16 index and a lower linoleic acid (LA) proportions in subcutaneous adipose tissue (SAT) than obesity-resistant rats. Desaturase indices were significantly correlated between many of the lipid fractions. The higher SCD-16 may indicate higher SCD-1 activity in SAT in OP rats, and combined with lower LA proportions may provide novel insights into HFD-induced obesity. The associations between desaturase indices show that plasma measurements can serve as proxies for some lipid fractions, but the correlations seem to be affected by diet and weight gain.