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Lopinavir/Ritonavir Impairs Physical Strength in Association with Reduced Igf1 Expression in Skeletal Muscle of Older Mice.

Wong S, Bhasin S, Serra C, Yu Y, Deng L, Guo W - J AIDS Clin Res (2013)

Bottom Line: Spontaneous movements were also reduced in Kaletra-treated old mice.Kaletra reduced IGF-1 expression in all muscle groups tested for the old and in cultured myotubes but to a less extent in the muscle of young animals.This effect was worse in older animals than in normal young adults.

View Article: PubMed Central - PubMed

Affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

ABSTRACT

Background: Late-middle age HIV patients are prone to fatigue despite effective viral control by antiretroviral therapies. Rodent models to recapitulate this phenotype are still not available.

Hypothesis: Drug treatment may compromise muscle strength and physical performance more in older individuals with pre-existing metabolic disorders than normal young ones.

Methods: Kaletra was given to overweight male mice at late-middle age and normal young adults; both on a rodent diet containing 30% fat calorie. Body composition and grip strength were measured at baseline and after drug treatment. Rota-rod running, insulin and glucose tolerance were measured at the end of the experiment. Drug effect on metabolic activity and spontaneous movements were assessed using the metabolic cage system. Representative muscle and fat tissue were analyzed for protein and mRNA expression. Selected findings were tested using murine C2C12 myotubes.

Results: Kaletra reduced grip strength in both young and older mice but impaired rotarod performance only in the old. Spontaneous movements were also reduced in Kaletra-treated old mice. Kaletra reduced IGF-1 expression in all muscle groups tested for the old and in cultured myotubes but to a less extent in the muscle of young animals. Reduced IGF-1 expression correlated with increased expression of muscle-specific atrogene MAFbx and MuRF1. Kaletra also increased abdominal fat mass markedly in the old animals and to a less extend in the young.

Conclusion: Long-term Kaletra intake aggravated abdominal obesity and impaired muscle strength. This effect was worse in older animals than in normal young adults.

No MeSH data available.


Related in: MedlinePlus

Effects of Kaletra on body composition, plasma and hepatic lipids, insulin and glucose tolerance(A) Liver weight, liver triglyceride concentration and plasma triglyceride concentration. (B). Tissue weight for major fat depots and hind limb muscle groups, expressed as percentage of body weight. (C) Glucose tolerance test. (D) Insulin tolerance test. Results are shown as means +/− se, N = 6 for each group. Between-group comparison was analyzed by Student‘s t test.
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Figure 2: Effects of Kaletra on body composition, plasma and hepatic lipids, insulin and glucose tolerance(A) Liver weight, liver triglyceride concentration and plasma triglyceride concentration. (B). Tissue weight for major fat depots and hind limb muscle groups, expressed as percentage of body weight. (C) Glucose tolerance test. (D) Insulin tolerance test. Results are shown as means +/− se, N = 6 for each group. Between-group comparison was analyzed by Student‘s t test.

Mentions: As shown in Figure 2A, liver weight was increased in mice treated with Kaletra but liver or plasma triglyceride concentrations were similar between the two groups, which were somewhat unexpected based on previous rodent studies [8–11], but nevertheless compatible with clinical reports that over 90% of the patients taking Kaletra don’t show dramatic increase in plasma lipids (< 12%) [14,15]. Kaletra has been shown to strikingly reduce fat mass in young mice [9,11]. However, in the old over-weighted mice used for this work, Kaleta caused a 40% increase in abdominal epididymal fat, without affecting inguinal fat (Figure 2B, upper panel). A decrease in perirenal fat mass was found (Figure s1), similar to that reported by others [11]. As shown in Figure 2B (lower panel), despite a decrease in grip strength and spontaneous activity, we were not able to detect any difference in muscle weight for gastrocnemius and quadriceps, two major weight-bearing muscles with different ratio of fast- and slow-twitching fibers, and tibialis anterior (TA) which consists of primarily fast-twitching myofibers. No significant difference was found in muscle fiber cross-sectional areas either after histological staining (data not shown). These results are in agreement with the clinical reports showing no correlation between lean mass and frailty in HIV patients taking anti-retrovirals [17].


Lopinavir/Ritonavir Impairs Physical Strength in Association with Reduced Igf1 Expression in Skeletal Muscle of Older Mice.

Wong S, Bhasin S, Serra C, Yu Y, Deng L, Guo W - J AIDS Clin Res (2013)

Effects of Kaletra on body composition, plasma and hepatic lipids, insulin and glucose tolerance(A) Liver weight, liver triglyceride concentration and plasma triglyceride concentration. (B). Tissue weight for major fat depots and hind limb muscle groups, expressed as percentage of body weight. (C) Glucose tolerance test. (D) Insulin tolerance test. Results are shown as means +/− se, N = 6 for each group. Between-group comparison was analyzed by Student‘s t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524660&req=5

Figure 2: Effects of Kaletra on body composition, plasma and hepatic lipids, insulin and glucose tolerance(A) Liver weight, liver triglyceride concentration and plasma triglyceride concentration. (B). Tissue weight for major fat depots and hind limb muscle groups, expressed as percentage of body weight. (C) Glucose tolerance test. (D) Insulin tolerance test. Results are shown as means +/− se, N = 6 for each group. Between-group comparison was analyzed by Student‘s t test.
Mentions: As shown in Figure 2A, liver weight was increased in mice treated with Kaletra but liver or plasma triglyceride concentrations were similar between the two groups, which were somewhat unexpected based on previous rodent studies [8–11], but nevertheless compatible with clinical reports that over 90% of the patients taking Kaletra don’t show dramatic increase in plasma lipids (< 12%) [14,15]. Kaletra has been shown to strikingly reduce fat mass in young mice [9,11]. However, in the old over-weighted mice used for this work, Kaleta caused a 40% increase in abdominal epididymal fat, without affecting inguinal fat (Figure 2B, upper panel). A decrease in perirenal fat mass was found (Figure s1), similar to that reported by others [11]. As shown in Figure 2B (lower panel), despite a decrease in grip strength and spontaneous activity, we were not able to detect any difference in muscle weight for gastrocnemius and quadriceps, two major weight-bearing muscles with different ratio of fast- and slow-twitching fibers, and tibialis anterior (TA) which consists of primarily fast-twitching myofibers. No significant difference was found in muscle fiber cross-sectional areas either after histological staining (data not shown). These results are in agreement with the clinical reports showing no correlation between lean mass and frailty in HIV patients taking anti-retrovirals [17].

Bottom Line: Spontaneous movements were also reduced in Kaletra-treated old mice.Kaletra reduced IGF-1 expression in all muscle groups tested for the old and in cultured myotubes but to a less extent in the muscle of young animals.This effect was worse in older animals than in normal young adults.

View Article: PubMed Central - PubMed

Affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

ABSTRACT

Background: Late-middle age HIV patients are prone to fatigue despite effective viral control by antiretroviral therapies. Rodent models to recapitulate this phenotype are still not available.

Hypothesis: Drug treatment may compromise muscle strength and physical performance more in older individuals with pre-existing metabolic disorders than normal young ones.

Methods: Kaletra was given to overweight male mice at late-middle age and normal young adults; both on a rodent diet containing 30% fat calorie. Body composition and grip strength were measured at baseline and after drug treatment. Rota-rod running, insulin and glucose tolerance were measured at the end of the experiment. Drug effect on metabolic activity and spontaneous movements were assessed using the metabolic cage system. Representative muscle and fat tissue were analyzed for protein and mRNA expression. Selected findings were tested using murine C2C12 myotubes.

Results: Kaletra reduced grip strength in both young and older mice but impaired rotarod performance only in the old. Spontaneous movements were also reduced in Kaletra-treated old mice. Kaletra reduced IGF-1 expression in all muscle groups tested for the old and in cultured myotubes but to a less extent in the muscle of young animals. Reduced IGF-1 expression correlated with increased expression of muscle-specific atrogene MAFbx and MuRF1. Kaletra also increased abdominal fat mass markedly in the old animals and to a less extend in the young.

Conclusion: Long-term Kaletra intake aggravated abdominal obesity and impaired muscle strength. This effect was worse in older animals than in normal young adults.

No MeSH data available.


Related in: MedlinePlus