Cold-Induced RNA-Binding Protein Promotes Glucose Metabolism and Reduces Apoptosis by Increasing AKT Phosphorylation in Mouse Skeletal Muscle Under Acute Cold Exposure

The main danger of cold stress to animals in cold regions is systemic metabolic changes and protein synthesis inhibition. Cold-induced RNA-binding protein is a cold shock protein that is rapidly up-regulated under cold stimulation in contrast to the inhibition of most proteins and participates in multiple cellular physiological activities by regulating targets. Therefore, this study was carried out to investigate the possible mechanism of CIRP-mediated glucose metabolism regulation and survival promotion in skeletal muscle after acute cold exposure. Skeletal muscle and serum from mice were obtained after 0, 2, 4 and 8 h of acute hypothermia exposure. Subsequently, the changes of CIRP, metabolism and apoptosis were examined. Acute cold exposure increased energy consumption, enhanced glycolysis, increased apoptosis, and up-regulated CIRP and phosphorylation of AKT. In addition, CIRP overexpression in C2C12 mouse myoblasts at each time point under 37°C and 32°C mild hypothermia increased AKT phosphorylation, enhanced glucose metabolism, and reduced apoptosis. CIRP knockdown by siRNA interference significantly reduced the AKT phosphorylation of C2C12 cells. Wortmannin inhibited the AKT phosphorylation of skeletal muscle after acute cold exposure, thereby inhibiting glucose metabolism and aggravating apoptosis. Taken together, acute cold exposure up-regulates CIRP in mouse skeletal muscle, which regulates glucose metabolism and maintains energy balance in skeletal muscle cells through the AKT signaling pathway, thus slowing down the apoptosis of skeletal muscle cells.

Cold-induced hyperphagia requires AgRP-neuron activation in mice

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity of in rats measured by 18F-FDG PET

Objective Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. The gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression. Conclusion Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.

Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity in rats measured by 18F-FDG PET

Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. the gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression.Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.

Protective Effects of Ginsenoside Rc Against Acute Cold Exposure Induced Myocardial Injury in Rats

Background: Ginsenoside Rc is one of the cardinal bioactive components of Panax ginseng that has been studied for various biological activities. This study aimed to investigate the protective effects of ginsenoside Rc against acute cold exposure induced myocardial injury in rats.Methods: The rats were intragastrically administrated with ginsenoside Rc (10, 20 mg/kg) or vehicle daily for 7 days. One hour after the seventh-day administration, 3% pentobarbital sodium was used to anesthetize the rats. Rats of the control group were kept in room temperature (22 ± 1 ℃) and the other groups of rats were exposed to low ambient temperature (-15 ± 1 ℃) in a cold chamber for 6 h. Cardiac function was monitored and recorded as well. To evaluate the protective effects of ginsenoside Rc, we also measured myocardial specific enzymes (lactate dehydrogenase, aspartate aminotransferase and creatine kinase-MB) in plasma, whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and hematocrit (HCT). The pathological changes of myocardium were observed through histopathological examination. The mRNA expression levels of TNF-α, IL-1β and IL-6 were by real-time quantitative PCR analysis. And the expressions of silent information regulator1 (SIRT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax) and Procaspase-3 in heart tissues were measured by Western blot method.Results: Ginsenoside Rc alone had no effect on cardiac function, myocardial enzyme activities and hemorheology in normal rats. Compared with the model group, pretreatment with ginsenoside Rc significantly improved cardiac function, diminished myocardial specific enzymes release and decreased erythrocyte aggregation index. As a result, the pretreatment regulated abnormal hemorheology, attenuated myocardial histological changes and structural abnormalities, reduced the mRNA expression levels of cardiac inflammatory markers. Ginsenoside Rc also resulted in up-regulating SIRT1, Bcl-2 and Procaspase-3 expressions and down-regulating Bax expression.Conclusion: The current study suggests that ginsenoside Rc alleviates acute cold exposure induced myocardial injury in rats by inhibiting cardiomyocyte apoptosis via SIRT1 and reducing inflammatory response.