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. 2022 May 9;23(9):5286.
doi: 10.3390/ijms23095286.

High-Fat Diet Impairs Muscle Function and Increases the Risk of Environmental Heatstroke in Mice

Matteo Serano  1   2 , Cecilia Paolini  1   3 , Antonio Michelucci  1 , Laura Pietrangelo  1   2 , Flavia A Guarnier  4 , Feliciano Protasi  1   2
Affiliations

High-Fat Diet Impairs Muscle Function and Increases the Risk of Environmental Heatstroke in Mice

Matteo Serano et al. Int J Mol Sci. .

Abstract

Environmental heat-stroke (HS) is a life-threatening response often triggered by hot and humid weather. Several lines of evidence indicate that HS is caused by excessive heat production in skeletal muscle, which in turn is the result of abnormal Ca2+ leak from the sarcoplasmic reticulum (SR) and excessive production of oxidative species of oxygen and nitrogen. As a high fat diet is known to increase oxidative stress, the objective of the present study was to investigate the effects of 3 months of high-fat diet (HFD) on the HS susceptibility of wild type (WT) mice. HS susceptibility was tested in an environmental chamber where 4 months old WT mice were exposed to heat stress (41 °C for 1 h). In comparison with mice fed with a regular diet, mice fed with HFD showed: (a) increased body weight and accumulation of adipose tissue; (b) elevated oxidative stress in skeletal muscles; (c) increased heat generation and oxygen consumption during exposure to heat stress; and finally, (d) enhanced sensitivity to both temperature and caffeine of isolated muscles during in-vitro contracture test. These data (a) suggest that HFD predisposes WT mice to heat stress and (b) could have implications for guidelines regarding food intake during periods of intense environmental heat.

Keywords: heat stroke; high-fat diet; malignant hyperthermia susceptibility; skeletal muscle.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Food intake, weight gain, and body fat mass. (A) Food intake during the 3 months of HFD treatment (1–4 months of age). (B) Weight gain during the 3 months of HFD treatment. (C,D) Representative dissection of the total adipose tissue, from Ctrl (D) vs. HFD (D) mice. (E) Amount of adipose tissue expressed as percentage of total body weight. Data are shown as mean ± SEM (** p < 0.01, as evaluated by two-tailed unpaired Student’s t-test). n = number of mice tested.
Figure 2
Figure 2
VO2 consumption, respiratory quotient (RQ), and basal energy expenditure during 24 h. (A) Oxygen consumption expressed as mL/min/kg0.75. (B) Respiratory quotient expressed as the ratio VCO2/VO2. (C) Area under the curve of 24 h-basal energy expenditure. Data are shown as mean ± SEM (* p < 0.05 and ** p < 0.01), as evaluated by two-way ANOVA followed by Tukey’s post-hoc test (panels (A,B)) and two-tailed unpaired Student’s t-test (panel (C)). n = number of mice tested.
Figure 3
Figure 3
Grip strength and in-vitro specific force. (A) Grip strength normalized to body weight (in mN/gr). (B,C) Force frequency (1–250 Hz) curve of specific (panel (B)) and relative force normalized to 250 Hz (panel (C)) in isolated EDL muscles. Data are shown as mean ± SEM (* p < 0.05 and ** p < 0.01), as evaluated by two-way ANOVA followed by Tukey’s post-hoc test (panel (B)) or two-tailed unpaired Student’s t-test (panel A). n = number of mice tested (in panel (A)). n = number of EDL muscles tested (in panels (B) and (C)).
Figure 4
Figure 4
Markers of oxidative stress in EDL muscles. Representative immunoblots (left) and relative band densities normalized to GAPDH levels (right) of 3-NT (panel (A)), SOD-1 (panel (B)), SOD-2 (panel (C)), and Catalase (panel (D)) in EDL muscle homogenates. Data are shown as mean ± SEM (* p < 0.05 and ** p < 0.01), as evaluated by two-tailed unpaired Student’s t-test. n = number of EDL muscles.
Figure 5
Figure 5
VO2 consumption, energy expenditure, and temperature recorded during heat stress protocol (41 °C for 1 h). (A) Oxygen consumption expressed as mL/min/kg0.75. (B) Area under the curve of 60 min energy expenditure. (C,D) Core and skin temperature, immediately before (T0) and at the end (Tf) the heat stress protocol. Data are shown as mean ± SEM (* p < 0.05 and ** p < 0.01), as evaluated by two-way ANOVA followed by Tukey’s post-hoc test (panel A) or two-tailed unpaired Student’s t-test (panels (B–D)). n = number of mice tested.
Figure 6
Figure 6
Temperature and caffeine dependence of basal tension in isolated EDL muscles. (A) Relative basal tension (normalized to 30 °C) during exposure to increasing temperature (from 30 to 44 °C). (B) Relative basal tension (normalized by 0 mM of caffeine) during exposure to increasing caffeine concentration (from 0 to 24 mM). Data are shown as mean ± SEM (* p < 0.05), as evaluated by two-way ANOVA followed by Tukey’s post-hoc test. n = number of EDL muscles tested.
Figure 7
Figure 7
Blood markers of skeletal muscle damage after the heat stress protocol (41 °C for 1 h). Level of K+ in plasma (mmol/L) (panel (A)); level of Ca2+ in plasma (nmol/L) (panel (B)); amount of creatine-kinase (U/L) in plasma (panel (C)). Data are shown as mean ± SEM (* p < 0.05), as evaluated by two-tailed unpaired Student’s t-test. n = number of mice tested.
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