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Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding.

De Andrade PB, Neff LA, Strosova MK, Arsenijevic D, Patthey-Vuadens O, Scapozza L, Montani JP, Ruegg UT, Dulloo AG, Dorchies OM - Front Physiol (2015)

Bottom Line: These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers.We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility.These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.

ABSTRACT
Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

No MeSH data available.


Related in: MedlinePlus

Expression levels of the iodothyronine deiodinases DIO1, DIO2, and DIO3 in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. The graphs show the expression levels of (A) DIO1, (B) DIO2, and (C) DIO3. The procedures for the normalization of the signals as well as the definition of the Pool and SOL extracts are described in the Legend to Figure 3. The position of the molecular weight markers (kDa) is shown on the right side of the blots. Asterisks indicate the bands that were identified as DIO1 and DIO3 proteins based on antibody validation experiments (see Supplementary Material for details). The faint extra bands likely represent non-specific labeling of other proteins. The ratios of DIO1-to-DIO3 (D), and DIO2-to-DIO3 (E), were calculated. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
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Figure 4: Expression levels of the iodothyronine deiodinases DIO1, DIO2, and DIO3 in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. The graphs show the expression levels of (A) DIO1, (B) DIO2, and (C) DIO3. The procedures for the normalization of the signals as well as the definition of the Pool and SOL extracts are described in the Legend to Figure 3. The position of the molecular weight markers (kDa) is shown on the right side of the blots. Asterisks indicate the bands that were identified as DIO1 and DIO3 proteins based on antibody validation experiments (see Supplementary Material for details). The faint extra bands likely represent non-specific labeling of other proteins. The ratios of DIO1-to-DIO3 (D), and DIO2-to-DIO3 (E), were calculated. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.

Mentions: Because net T3 neogenesis is the result of T3 synthesis from T4 (through deiodination catalyzed by DIO1 and/or DIO2) and T3 degradation by DIO3, we analyzed the expression of the deiodinases DIO1, DIO2 and DIO3 in gastrocnemius muscles (Figure 4). As shown in Supplementary Material, we perform an extensive validation of the antibodies used for Western-blot analysis of DIO expression in rat skeletal muscle. We found that DIO1 and DIO3 were more abundant (+38% and +71%, respectively), whereas DIO2 was less abundant (−16%) in gastrocnemius muscle after semistarvation (Figures 4A–C). These differences were all highly significant and partly persisted after refeeding (+28%, −13%, and +25% for DIO1, DIO2, and DIO3, respectively). As a consequence of these differential changes in DIO levels, the relative DIO1-to-DIO3 ratio was not significantly affected by semistarvation (Figure 4D), whereas the DIO2-to-DIO3 ratio was strongly diminished to ~48% of the control value and was only partly corrected to normal values after refeeding (Figure 4E). These alterations in DIO levels likely accounted for the diminished local net T3 neogenesis in gastrocnemius muscles.


Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding.

De Andrade PB, Neff LA, Strosova MK, Arsenijevic D, Patthey-Vuadens O, Scapozza L, Montani JP, Ruegg UT, Dulloo AG, Dorchies OM - Front Physiol (2015)

Expression levels of the iodothyronine deiodinases DIO1, DIO2, and DIO3 in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. The graphs show the expression levels of (A) DIO1, (B) DIO2, and (C) DIO3. The procedures for the normalization of the signals as well as the definition of the Pool and SOL extracts are described in the Legend to Figure 3. The position of the molecular weight markers (kDa) is shown on the right side of the blots. Asterisks indicate the bands that were identified as DIO1 and DIO3 proteins based on antibody validation experiments (see Supplementary Material for details). The faint extra bands likely represent non-specific labeling of other proteins. The ratios of DIO1-to-DIO3 (D), and DIO2-to-DIO3 (E), were calculated. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
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Figure 4: Expression levels of the iodothyronine deiodinases DIO1, DIO2, and DIO3 in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. The graphs show the expression levels of (A) DIO1, (B) DIO2, and (C) DIO3. The procedures for the normalization of the signals as well as the definition of the Pool and SOL extracts are described in the Legend to Figure 3. The position of the molecular weight markers (kDa) is shown on the right side of the blots. Asterisks indicate the bands that were identified as DIO1 and DIO3 proteins based on antibody validation experiments (see Supplementary Material for details). The faint extra bands likely represent non-specific labeling of other proteins. The ratios of DIO1-to-DIO3 (D), and DIO2-to-DIO3 (E), were calculated. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
Mentions: Because net T3 neogenesis is the result of T3 synthesis from T4 (through deiodination catalyzed by DIO1 and/or DIO2) and T3 degradation by DIO3, we analyzed the expression of the deiodinases DIO1, DIO2 and DIO3 in gastrocnemius muscles (Figure 4). As shown in Supplementary Material, we perform an extensive validation of the antibodies used for Western-blot analysis of DIO expression in rat skeletal muscle. We found that DIO1 and DIO3 were more abundant (+38% and +71%, respectively), whereas DIO2 was less abundant (−16%) in gastrocnemius muscle after semistarvation (Figures 4A–C). These differences were all highly significant and partly persisted after refeeding (+28%, −13%, and +25% for DIO1, DIO2, and DIO3, respectively). As a consequence of these differential changes in DIO levels, the relative DIO1-to-DIO3 ratio was not significantly affected by semistarvation (Figure 4D), whereas the DIO2-to-DIO3 ratio was strongly diminished to ~48% of the control value and was only partly corrected to normal values after refeeding (Figure 4E). These alterations in DIO levels likely accounted for the diminished local net T3 neogenesis in gastrocnemius muscles.

Bottom Line: These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers.We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility.These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.

ABSTRACT
Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

No MeSH data available.


Related in: MedlinePlus