PMC:7432599 / 19967-25427 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7432599","sourcedb":"PMC","sourceid":"7432599","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7432599","text":"2.5. The Anti-Inflammatory Fatty Acid Profile of Goat Milk’s Prevents Hepatic Lipid Deposition and Inflammatory Markers and Increases AMPK Phosphorylation\nExcessive lipid deposition in liver induces cytotoxic cell death and inflammation, leading to the progression of non-alcoholic fatty liver disease to steatohepatitis. However, dietary fatty acid composition can modify hepatic lipid metabolism and the inflammatory response. Long-chain saturated fatty acids such as stearic acid favors lipid accumulation and inflammation whereas long-chain n-3 polyunsaturated fatty acids such as eicosapentaenoic (EPA), docosahexaenoic (DHA) and rumen bacteria-derived conjugated linoleic acid (CLA) exerts anti-inflammatory activities in liver [23].\nTo evaluate if the fatty acid profile in liver reflects that of experimental diets, we determined the fatty acid profile of experimental diets and liver. The most abundant saturated fatty acids in goat milk are the short-chain myristic (C14:0), capric (C8:0) and the long-chain stearic (C18:0). Regardless of the origin of the goat milk, all diets containing goat’s milk showed a greater amount of myristic and capric acids with respect to control or HF (Figure 6A,B). Moreover, the amount of stearic acid in diets containing goat’s milk was lower compared to the HF diet (Figure 6C). This pattern was reflected in the fatty acids present in the liver (Figure 6A–C). The level of the pro-inflammatory fatty acid arachidonic acid was lower in the diets containing goat’s milk than in HF or control (Figure 6D). Hepatic arachidonic acid levels presented the same pattern. Moreover, the levels of EPA and CLA were higher in the diets that contains goat milk with respect to HF or control (Figure 6E,F), which was reflected in the hepatic content of these fatty acids. These results indicate that hepatic fatty acid composition reflects the composition of dietary fatty acids and suggest that goat’s milk fatty acid profile could exert beneficial effects in liver such as reduced lipid accumulation and lower inflammation.\nThe primary source of hepatic fat due to calorie excess is de novo lipogenesis mediated by the activity of the sterol regulatory element binding protein-1c (SREBP-1c). This transcription factor mediates gene expression of lipogenic enzymes in the liver [24]. To evaluate the effect of goat milk intake on the development of fatty liver and SREBP-1c expression, H\u0026E and ORO staining and real-time PCR quantification of SREBP-1c mRNA were performed on liver samples from the different experimental groups. As expected, mice fed HF presented a high number of hepatocytes containing enlarged lipid vacuoles (Figure 6G). Accordingly, densitometric quantification of ORO staining revealed a significant increase in lipid content of liver of HF mice with respect to control (Figure 6H). Notably, mice fed with the HFCD, HFG and HFAF diets showed less fat accumulation in liver and cytostructural features similar to those of control mice. Messenger RNA abundance of SREBP-1c was higher in the liver of mice fed HF with respect to control (Figure 6I). Strikingly, SREBP-1c gene expression was lower in the liver of animals fed with HFCD, HFG and HFAF diets with respect to HF. The expression of SREBP-1c in liver increases in response to hyperinsulinemia/insulin resistance but is reduced by particular fatty acids such as EPA and DHA [25]. Accordingly, SREBP-1c mRNA abundance in liver was inversely correlated with hepatic DHA content (Figure 6J). Another beneficial effect of the fatty acids presents in goat’s milk, such as EPA is the activation of AMPK, the cellular energy sensor [26]. Upon activation, AMPK increases glucose and fatty acid oxidation, reducing lipid content in liver [27]. As observed in Figure 6K,L, HFG and HFAF increased AMPK phosphorylation in liver with respect to the rest of the experimental diets (Figure 6K). These results indicate that consumption of goat’s milk in mice fed a HF diet prevents hepatic steatosis in part by reducing SREBP-1c-mediated lipogenesis and, simultaneously, by increasing AMPK-mediated lipid oxidation.\nBesides the increase in lipogenesis, an increase in hepatic oxidative and endoplasmic reticulum stress are determining factors in the development of non-alcoholic fatty liver disease by activating JNK phosphorylation, a common downstream element in oxidative and endoplasmic reticulum stress signaling pathways [28]. As observed in Figure 6K,M, the abundance of phosphorylated JNK was higher in liver of mice fed HF with respect to control. Notably, HFCD, HFG and HFAF fed mice presented lower levels of p-JNK than those observed in HF. To evaluate if the reduced JNK phosphorylation was associated with lesser intrahepatic TNF-α content, we determined this cytokine in liver homogenates. Accordingly, TNF-α abundance was higher in liver homogenates of HF mice with respect to control, HFCD, HFG and HFAF (Figure 6N).\nFinally, we determined the hepatic EPA+DHA/AA ratio. This ratio is used as an anti-inflammatory index, where a higher ratio indicates a protective role in the development of inflammatory states [29]. Notably, mice fed goat’s milk presented a significant higher hepatic EPA+DHA/AA ratio with respect to those fed HF or control (Figure 6O). These results indicate that goat’s milk intake prevents hepatic inflammation in mice fed a HF associated to a protective proportion of n-3/n-6 long chain polyunsaturated fatty acids in liver.","divisions":[{"label":"title","span":{"begin":0,"end":154}},{"label":"p","span":{"begin":155,"end":739}},{"label":"p","span":{"begin":740,"end":2058}},{"label":"p","span":{"begin":2059,"end":4111}},{"label":"p","span":{"begin":4112,"end":4929}}],"tracks":[{"project":"2_test","denotations":[{"id":"32752280-18306430-52426008","span":{"begin":735,"end":737},"obj":"18306430"},{"id":"32752280-30271747-52426009","span":{"begin":2313,"end":2315},"obj":"30271747"},{"id":"32752280-27863448-52426010","span":{"begin":3387,"end":3389},"obj":"27863448"},{"id":"32752280-22739758-52426011","span":{"begin":3742,"end":3744},"obj":"22739758"},{"id":"32752280-25132496-52426012","span":{"begin":4424,"end":4426},"obj":"25132496"},{"id":"32752280-25173718-52426013","span":{"begin":5125,"end":5127},"obj":"25173718"},{"id":"T98644","span":{"begin":735,"end":737},"obj":"18306430"},{"id":"T5291","span":{"begin":2313,"end":2315},"obj":"30271747"},{"id":"T23424","span":{"begin":3387,"end":3389},"obj":"27863448"},{"id":"T78773","span":{"begin":3742,"end":3744},"obj":"22739758"},{"id":"T28876","span":{"begin":4424,"end":4426},"obj":"25132496"},{"id":"T4392","span":{"begin":5125,"end":5127},"obj":"25173718"}],"attributes":[{"subj":"32752280-18306430-52426008","pred":"source","obj":"2_test"},{"subj":"32752280-30271747-52426009","pred":"source","obj":"2_test"},{"subj":"32752280-27863448-52426010","pred":"source","obj":"2_test"},{"subj":"32752280-22739758-52426011","pred":"source","obj":"2_test"},{"subj":"32752280-25132496-52426012","pred":"source","obj":"2_test"},{"subj":"32752280-25173718-52426013","pred":"source","obj":"2_test"},{"subj":"T98644","pred":"source","obj":"2_test"},{"subj":"T5291","pred":"source","obj":"2_test"},{"subj":"T23424","pred":"source","obj":"2_test"},{"subj":"T78773","pred":"source","obj":"2_test"},{"subj":"T28876","pred":"source","obj":"2_test"},{"subj":"T4392","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#eccf93","default":true}]}]}}