Metformin, pioglitazone, dapagliflozin and their combinations ameliorate manifestations associated with NAFLD in rats via anti-inflammatory, anti-fibrotic, anti-oxidant and anti-apoptotic mechanisms

et al. 2023

Preprint

The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption with development of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 hours consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. Therefore, we conclude that regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.

Section: Discussionmentioning

confidence: 99%

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6J mice

et al. 2023

Preprint

“…Here, we showed that oGTT impairment induced by acute (24 h) HFHS diet was reversed after 24 h of regular chow ingestion. The reversal of diet-induced insulin resistance can be achieved by changing diet, promoting physical exercise, pharmacologically, among other approaches 40 – 42 . However, this reversal is a time-dependent process that also depends on the severity of the condition 43 .…”

Section: Discussionmentioning

confidence: 99%

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6 J mice

et al. 2023

Sci Rep

The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption with development of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 h consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. Therefore, we conclude that regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.

“…Here, we showed that oGTT impairment induced by acute (24 hours) HFHS diet was reversed after 24 hours of regular chow ingestion. The reversal of diet-induced insulin resistance can be achieved by changing diet, promoting physical exercise, pharmacologically, among other approaches [45][46][47]. However, this reversal is a time-dependent process that also depends on the severity of the condition [48].…”

Section: Discussionmentioning

confidence: 99%

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6J mice

et al. 2022

Preprint

BACKGROUNDS: The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption withdevelopment of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies, aiming to identify putative targets for treatments. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. METHODS: Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. RESULTS: Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 hours consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. CONCLUSIONS: Regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.