Limits...
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 selected proteins in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. (A) Amount of myosin heavy chains (MyHC) were determined by Coomassie staining in 3 independents experiments. MyHC were similarly abundant in all 4 groups and were thus validated as internal controls for the quantification of the other muscle markers under study. Selected proteins that are well known markers of Ca2+ handling in slow-twitch or fast-twitch fibers were analyzed: (B) SERCA1, (C) SERCA2, (D) calsequestrin 1, (E) calsequestrin 2, and (F) parvalbumin. The abundance of transcription factors that control the development of slow-twitch muscles either positively or negatively were also determined: (G) calcineurin, (H) PGC1-α (the most intense band at the expected size for the full-length protein was analyzed; the smaller molecular weight bands likely to be degradation products were excluded), and (I) FoxO1 (all bands, likely representing native, methylated, and acetylated forms, were quantified). The signals (B–I) were corrected for their MyHC content and normalized to the signal of a pool sample (a mixture of aliquots of all extracts) loaded on the gels for the purpose of intra-gel and inter-gel comparison. The signals from an extract of soleus muscle (a slow-twitch muscle), referred to as SOL, are shown for comparison. They were acquired under the same exposure condition as the experimental groups. The position of the molecular weight markers (kDa) is shown on the right side of the blots. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4584973&req=5

Figure 3: Expression levels of selected proteins in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. (A) Amount of myosin heavy chains (MyHC) were determined by Coomassie staining in 3 independents experiments. MyHC were similarly abundant in all 4 groups and were thus validated as internal controls for the quantification of the other muscle markers under study. Selected proteins that are well known markers of Ca2+ handling in slow-twitch or fast-twitch fibers were analyzed: (B) SERCA1, (C) SERCA2, (D) calsequestrin 1, (E) calsequestrin 2, and (F) parvalbumin. The abundance of transcription factors that control the development of slow-twitch muscles either positively or negatively were also determined: (G) calcineurin, (H) PGC1-α (the most intense band at the expected size for the full-length protein was analyzed; the smaller molecular weight bands likely to be degradation products were excluded), and (I) FoxO1 (all bands, likely representing native, methylated, and acetylated forms, were quantified). The signals (B–I) were corrected for their MyHC content and normalized to the signal of a pool sample (a mixture of aliquots of all extracts) loaded on the gels for the purpose of intra-gel and inter-gel comparison. The signals from an extract of soleus muscle (a slow-twitch muscle), referred to as SOL, are shown for comparison. They were acquired under the same exposure condition as the experimental groups. The position of the molecular weight markers (kDa) is shown on the right side of the blots. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.

Mentions: We investigated whether the slower kinetics of contraction and relaxation were accompanied by alterations in the expression of selected markers of slow vs. fast fibers in rat gastrocnemius (Figure 3). The expression levels of SERCA pumps and of the calcium-buffering proteins, CSQ1, CSQ2, and parvalbumin were normalized to that of total MyHC (Figure 3A). The level of SERCA1 (specific for fast muscle fibers) tended to increase after semistarvation and refeeding, although the inter group differences were not significant (Figure 3B). SERCA2, which is specific for type I fibers, found predominantly in slow muscles, was significantly decreased after semistarvation; an effect that was completely reversed by refeeding (Figure 3C). As shown in Figures 3D–F, semistarvation and refeeding had no impact on the abundance of the fast muscle-specific markers CSQ1 and parvalbumin or on the slow muscle-specific marker CSQ2.


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 selected proteins in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. (A) Amount of myosin heavy chains (MyHC) were determined by Coomassie staining in 3 independents experiments. MyHC were similarly abundant in all 4 groups and were thus validated as internal controls for the quantification of the other muscle markers under study. Selected proteins that are well known markers of Ca2+ handling in slow-twitch or fast-twitch fibers were analyzed: (B) SERCA1, (C) SERCA2, (D) calsequestrin 1, (E) calsequestrin 2, and (F) parvalbumin. The abundance of transcription factors that control the development of slow-twitch muscles either positively or negatively were also determined: (G) calcineurin, (H) PGC1-α (the most intense band at the expected size for the full-length protein was analyzed; the smaller molecular weight bands likely to be degradation products were excluded), and (I) FoxO1 (all bands, likely representing native, methylated, and acetylated forms, were quantified). The signals (B–I) were corrected for their MyHC content and normalized to the signal of a pool sample (a mixture of aliquots of all extracts) loaded on the gels for the purpose of intra-gel and inter-gel comparison. The signals from an extract of soleus muscle (a slow-twitch muscle), referred to as SOL, are shown for comparison. They were acquired under the same exposure condition as the experimental groups. The position of the molecular weight markers (kDa) is shown on the right side of the blots. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4584973&req=5

Figure 3: Expression levels of selected proteins in gastrocnemius extracts from semistarved and refed rats and their respective controls were determined by Western blots. (A) Amount of myosin heavy chains (MyHC) were determined by Coomassie staining in 3 independents experiments. MyHC were similarly abundant in all 4 groups and were thus validated as internal controls for the quantification of the other muscle markers under study. Selected proteins that are well known markers of Ca2+ handling in slow-twitch or fast-twitch fibers were analyzed: (B) SERCA1, (C) SERCA2, (D) calsequestrin 1, (E) calsequestrin 2, and (F) parvalbumin. The abundance of transcription factors that control the development of slow-twitch muscles either positively or negatively were also determined: (G) calcineurin, (H) PGC1-α (the most intense band at the expected size for the full-length protein was analyzed; the smaller molecular weight bands likely to be degradation products were excluded), and (I) FoxO1 (all bands, likely representing native, methylated, and acetylated forms, were quantified). The signals (B–I) were corrected for their MyHC content and normalized to the signal of a pool sample (a mixture of aliquots of all extracts) loaded on the gels for the purpose of intra-gel and inter-gel comparison. The signals from an extract of soleus muscle (a slow-twitch muscle), referred to as SOL, are shown for comparison. They were acquired under the same exposure condition as the experimental groups. The position of the molecular weight markers (kDa) is shown on the right side of the blots. SS, semistarved rats; CSS, control of semistarved rats; RF, refed rats; CRF, control of refed rats. n = 10; Mann-Whitney test; **P ≤ 0.01; ***P ≤ 0.001; ns, not significant, comparing SS or RF to their respective control.
Mentions: We investigated whether the slower kinetics of contraction and relaxation were accompanied by alterations in the expression of selected markers of slow vs. fast fibers in rat gastrocnemius (Figure 3). The expression levels of SERCA pumps and of the calcium-buffering proteins, CSQ1, CSQ2, and parvalbumin were normalized to that of total MyHC (Figure 3A). The level of SERCA1 (specific for fast muscle fibers) tended to increase after semistarvation and refeeding, although the inter group differences were not significant (Figure 3B). SERCA2, which is specific for type I fibers, found predominantly in slow muscles, was significantly decreased after semistarvation; an effect that was completely reversed by refeeding (Figure 3C). As shown in Figures 3D–F, semistarvation and refeeding had no impact on the abundance of the fast muscle-specific markers CSQ1 and parvalbumin or on the slow muscle-specific marker CSQ2.

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