expression of peroxisome-proliferator-activated receptor alpha ( Ppara ) via activation of AMP-activated, alpha 2 catalytic subunit ( Prkaa2 ) in hepatocytes. This metabolic response increased fatty acid oxidation enzymes such as acyl-CoA oxidase (ACO) and
Alia H Sukkar, Aaron M Lett, Gary Frost and Edward S Chambers
Sabina Paglialunga, Patrick Schrauwen, Christian Roy, Esther Moonen-Kornips, Huiling Lu, Matthijs K C Hesselink, Yves Deshaies, Denis Richard and Katherine Cianflone
) with no change in skeletal muscle GLUT-4 protein levels as assessed by western analysis (data not shown). Evaluation of fatty acid oxidation The increased food intake despite similar weight gain in C5L2KO-LF mice
Karen R Kelly, Chin K Sung, Marcia J Abbott and Lorraine P Turcotte
( Salteil & Kahn 2001 ). More recently, in muscle perfused or incubated with glucose, insulin has also been shown to decrease long-chain fatty acid (LCFA) oxidation, increase triacylglycerol (TG) synthesis, and increase LCFA uptake via translocation of the
MC Sugden, HS Lall, RA Harris and MJ Holness
The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.
M Furuhashi, N Ura, H Murakami, M Hyakukoku, K Yamaguchi, K Higashiura and K Shimamoto
We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acid-binding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a beta-oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of beta-oxidation in muscles.
J. PEARCE and D. BALNAVE
The increases in liver and blood lipid contents which occur at the onset of lay in the fowl can be simulated in the immature pullet by oestrogen administration (Lorenz, 1954). The liver is the major site of lipogenesis (Goodridge, 1968) and also of oestrogen-induced lipaemia (Ranney & Chaikoff, 1951). Androgens and progestagens are also involved in the physiological changes encountered at point-of-lay (see Balnave & Pearce, 1974) but neither affects the total blood or liver lipid content. Balnave (1968, 1969) suggested that testosterone and progesterone can influence hepatic lipid metabolism and gonadal hormones other than oestrogens can affect hepatic lipogenic enzyme activities (Pearce & Balnave, 1973; Balnave & Pearce, 1974). The present experiments investigated the hypothesis (Balnave, 1968) that gonadal hormones may also affect lipid degradation.
Four-week-old pullets, given food and water ad libitum, received i.m. injections, in 0·2 ml corn oil, of either 2 mg oestradiol dipropionate, 2 mg