The effects of diet and chronic exercise on skeletal muscle ghrelin response

Regulation of peripheral tissue substrate metabolism by the gut-derived hormone ghrelin

“…In mice, daily injections of AG reduce whole-body lipid utilization, measured as an increase in the respiratory exchange ratio [ 83 ]. Despite this initial finding suggesting a reduction in muscle fat use with ghrelin, a number of studies from our lab have demonstrated both AG and unAG to directly stimulate palmitate oxidation in isolated glycolytic [ 15 ] and oxidative [ 15 , [75] , [76] , [77] ] muscles. Both ghrelin isoforms have a protective effect on insulin-stimulated glucose uptake under high palmitate conditions that would normally result in impaired insulin signaling [ 75 , 97 ].…”

“…The inconsistency in these findings may indicate a potential dissociation between the acute and more chronic effects of AG on skeletal muscle glucose metabolism. Improvement of insulin sensitivity observed with chronic treatment may be due in part to the effects of ghrelin on lipid metabolism and inflammation [ 9 , 15 , [75] , [76] , [77] , [78] ]. This will be discussed later in the review.…”

Stimulation of fat oxidation in rat muscle by unacylated ghrelin persists for 2–3 hours, but is independent of fatty acid transporter translocation

“…One general limitation is the supraphysiological dose of UnAG used in our interventions. Our dosage is in line with that previously used in our lab as well as others (Barazzoni et al, 2005;Cervone et al, 2020;Kraft et al, 2019;Lovell et al, 2022) and chosen to elicit a maximal response. We observed no differences in fatty acid oxidation between any of the isolated muscle UnAG exposure conditions despite different lengths of exposure and timing; thus, our supraphysiological dose may have elicited a maximal response and made it difficult to analyze any changes between treatment groups.…”

“…In humans, UnAG injection can reduce circulating fatty acid levels in a subsequent test-meal and improve insulin sensitivity (Benso et al, 2012;Gauna et al, 2004). Our lab has previously demonstrated that UnAG is a significant stimulator of fatty acid oxidation in isolated rat skeletal muscle (Cervone et al, 2020;Kraft et al, 2019;Lovell et al, 2022). An important step in the regulation of muscle fatty acid oxidation is governed by CPT1 which regulates the entry of fatty acids into the mitochondria.…”

“…2.3.1 | Isolated soleus incubations for assessment of palmitate oxidation Assessment of palmitate oxidation was as previously reported from our laboratory using 14 C-palmitate (Cervone et al, 2020;Kraft et al, 2019;Lovell et al, 2022). Briefly, soleus muscle strips were excised tendon-to-tendon and placed in pre-gassed vials (95% O 2 ; 5% CO 2 ) in a warmed (30°C) shaking water bath.…”