Marc A. Tuazon

Postprandial triglyceride and free fatty acid metabolism in obese women after either endurance or resistance exercise

We investigated the effects of two exercise modalities on postprandial triglyceride (TG) and free fatty acid (FFA) metabolism. Sedentary, obese women were studied on three occasions in randomized order: endurance exercise for 60 min at 60-65% aerobic capacity (E), ~60 min high-intensity resistance exercise (R), and a sedentary control trial (C). After exercise, a liquid-mixed meal containing [U-(13)C]palmitate was consumed, and subjects were studied over 7 h. Isotopic enrichment (IE) of plasma TG, plasma FFA, and breath carbon dioxide compared with meal IE indicated the contribution of dietary fat to each pool. Total and endogenously derived plasma TG content was reduced significantly in both E and R compared with C (P < 0.05), with no effect of exercise on circulating exogenous (meal-derived) TG content. Exogenous plasma FFA content was increased significantly following both E and R compared with C (P < 0.05), whereas total and endogenous FFA concentrations were elevated only in E (P < 0.05) compared with C. Fatty acid (FA) oxidation rates were increased significantly after E and R compared with C (P < 0.05), with no difference between exercise modalities. The present results indicate that E and R may be equally effective in reducing postprandial plasma TG concentration and enhancing lipid oxidation when the exercise sessions are matched for duration rather than for energy expenditure. Importantly, tracer results indicated that the reduction in postprandial lipemia after E and R exercise bouts is not achieved by enhanced clearance of dietary fat but rather, is achieved by reduced abundance of endogenous FA in plasma TG.

Fatty acid profile of skeletal muscle phospholipid is altered in mdx mice and is predictive of disease markers

The mdx mouse is a model for Duchenne muscular dystrophy. The fatty acid (FA) composition in dystrophic muscle could potentially impact the disease severity. We tested FA profiles in skeletal muscle phospholipid (PL) and triglyceride in mdx and control (con) mice to assess associations with disease state as well as correlations with grip strength (which is lower in mdx) and serum creatine kinase (CK, which is elevated in mdx). Compared with con, mdx PL contained less docosahexaenoic acid (P < .001) and more linoleic acid (P = .001). Docosahexaenoic acid contents did not correlate with strength or serum CK. Linoleic acid content in PL was positively correlated with CK in mdx (P < .05) but not con. α-Linolenic acid content in PL was positively correlated with strength in mdx (P < .05) but not con. The FA profile in triglyceride showed less difference between groups and far less predictive ability for disease markers. We conclude that profiling the FA composition of tissue lipids (particularly PL) can be a useful strategy for generating novel biomarkers and potential therapeutic targets in muscle diseases and likely other pathological conditions as well. Specifically, the present results have indicated potential benefits of raising content of particular n-3 FAs (especially α-linolenic acid) and reducing content of particular n-6 FAs (linoleic acid) in PL of dystrophic muscle.

Separation of positional and geometrical fatty acid isomers as 2-nitrophenylhydrazide derivatives by high-performance liquid chromatography.

Previously, following derivatization to their 2-nitrophenylhydrazide (2-NPH) derivatives, fatty acid (FA) abundances have been evaluated using high-performance liquid chromatography (HPLC). Although the method was sensitive, resolution was insufficient for many of the biologically important FAs. We have developed an enhanced separation of 24 FAs by use of different column temperature, stationary phase, and mobile phase gradient conditions. We applied this method to analysis of mouse skeletal muscle phospholipid and triglyceride. This further development of the chromatographic separation of 2-NPH FAs may lead to greater utility of this HPLC approach.

Intensity-dependent and sex-specific alterations in hepatic triglyceride metabolism in mice following acute exercise

Precise regulation of hepatic triglyceride (TG) metabolism and secretion is critical for health, and exercise could play a significant role. We compared one session of high-intensity interval exercise (HIIE) vs. continuous exercise (CE) on hepatic TG metabolism. Female and male mice were assigned to CE, HIIE, or sedentary control (CON). HIIE was a 30-min session of 30-s running intervals (30 m/min) interspersed with 60-s walking periods (5 m/min). CE was a distance- and duration-matched run at 13.8 m/min. Hepatic content of TG and TG secretion rates, as well as expression of relevant genes/proteins, were measured at 3 h (day 1) and 28 h (day 2) postexercise. On day 1, hepatic [TG] in CE and HIIE were both elevated vs. CON in both sexes with an approximately twofold greater elevation in HIIE vs. CE in females. In both sexes, hepatic perilipin 2 (PLIN2) protein on day 1 was increased significantly by both exercise types with a significantly greater increase with HIIE than CE, whereas the increase in mRNA reached significance only after HIIE. On day 2 in both sexes the increases in hepatic TG and PLIN2 with exercise declined toward CON levels. Only HIIE on day 2 resulted in reduced hepatic TG secretion by ∼20% in females with no effect in males. Neither exercise modality altered AMPK signaling or microsomal triglyceride transfer protein expression. Females exhibited higher hepatic TG secretion than males in association with different expression levels of related metabolic enzymes. These intensity-dependent and sex-specific alterations following exercise may have implications for sex-based exercise prescription.

Effects of ovariectomy and exercise training intensity on energy substrate and hepatic lipid metabolism, and spontaneous physical activity in mice

BACKGROUND Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. METHODS Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. RESULTS Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. CONCLUSIONS The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice.

Fatty Acid Profile of Cardiac Muscle Phospholipid and Triacylglycerol in MDX Mice and C57BL/10ScSnJ Controls

The mdx mouse is a model for Duchenne muscular dystrophy (DMD), a debilitating disease affecting striated muscle. It is established that the fatty acid (FA) composition of skeletal muscle phospholipid (PL) is altered in mdx mice, but it is not known if cardiac muscle is similarly affected by dystrophin-deficiency. We tested FA profiles in PL and triacylglycerol (TAG) in cardiac muscle of 12-week old mdx and control (con) mice. Of 22 different FA, similar to our previous finding for skeletal muscle, the most abundant FA in heart PL were palmitic, stearic, cis-vaccenic, linoleic, and docosahexaenoic acid, while for TAG the most abundant FA were palmitic, oleic, cis-vaccenic, and linoleic acid. In comparing mdx and con, no significant group differences were detected for any FA in PL or TAG. Thus, unlike skeletal muscle, FA composition in cardiac muscle PL is not different between mdx and con at the age studied. The results can be understood in the context of tissue-specific disease severity in mdx mice, as pathology is quite modest in cardiac compared with skeletal muscle.