A gender and culturally specific approach to reduce NAFLD in Mexican American men

摘要 需要有效的治疗干预措施来遏制非酒精性脂肪肝的惊人增长 墨西哥裔美国人中的疾病(NAFLD)，这是一个研究不足的人群，患上 肝细胞癌(HCC)。NAFLD的主要生活方式危险因素包括缺乏运动和糖分- 甜味饮料消费，这一特点在墨西哥裔美国男性中得到了高度体现。这个 墨西哥裔美国男性患非酒精性脂肪肝的风险进一步增加，风险的频率更高(高达55%) PNPLA3(Patatin样磷脂酶结构域包含蛋白)基因的等位基因。这个等位基因赋予了一种 非酒精性脂肪肝和肝细胞癌的易感性大大增加。在没有FDA批准的药物的情况下 药物、生活方式改变，包括通过改善饮食和体力活动而开始的减肥 行为，是预防和治疗非酒精性脂肪肝的推荐疗法。生活方式干预 以适度减肥为目标(大约5%的体重)已被证明会导致显著的 减少肝脏脂肪。然而，关于专门设计的生活方式干预效果的证据 对于风险更大的非酒精性脂肪肝的墨西哥裔美国男性，目前还没有。大卫·加西亚医生有一种 良好的生活方式干预基础，为他迈向目标奠定了良好的基础 减少墨西哥裔美国男性的肥胖相关疾病负担。这款NIMHD K01的目标是 研究科学家发展奖是为加西亚博士提供对代谢的深入了解 以及肥胖相关癌症和相关疾病的致病途径和危险因素，并有特定的重点 墨西哥裔美国男性非酒精性脂肪肝和肝癌的研究。他还将接受非侵入性成像生物标记物方面的培训 (例如，瞬时弹性成像)，用于评估和管理疾病状态和风险因素。最后，他 将促进他在研究方法方面的知识和技能发展(例如，定量分析和 定性研究)为设计和定制特定文化的研究提供信息，以减轻 NAFLD。在辛西娅·汤姆森博士和迈克尔·法伦博士的指导下，共同导师和合作者； 对于提议的项目，加西亚博士打算1)使用卡梅伦县西语裔美国人可用的数据集 队列(CCHC)评估NAFLD的风险，包括表型因素(生活方式行为)在 墨西哥裔美国男性；2)评估肥胖相关癌症风险的知识、态度和信念， 强调非酒精性脂肪肝和墨西哥裔美国男性的肝癌风险；以及3)评估可行性、可接受性、 为墨西哥裔美国男性量身定做的NAFLD减肥干预措施的初步疗效。这个 此K01应用程序中的培训计划和研究策略将为加西亚博士提供时间、资源和 实现他的职业目标所必需的导师关系，亚利桑那大学热情支持 领导者和极其适当和支持性的研究环境。

ABSTRACT Effective therapeutic interventions are needed to stem the alarming increases in non-alcoholic fatty liver disease (NAFLD) in Mexican-American men, an understudied population at greater risk for the development of hepatocellular carcinoma (HCC). Primary lifestyle risk factors for NAFLD include physical inactivity and sugar- sweetened beverage consumption, characteristics that are highly evidenced in Mexican-American men. The risk of NAFLD is further increased in Mexican-American men by a greater frequency (up to 55%) of the risk allele at the PNPLA3 (patatin-like phospholipase domain-containing protein) gene. This allele confers a substantially greater susceptibility to NAFLD and HCC. In the absence of FDA-approved pharmaceutical agents, lifestyle modification, including weight loss initiated by improvements in dietary and physical activity behavior, is the recommended therapy for the prevention and treatment of NAFLD. Lifestyle interventions targeting modest weight loss (approximately 5% body weight) have been shown to result in significant reductions in liver fat. However, evidence regarding the effects of a lifestyle intervention designed exclusively for Mexican-American men at greater risk for NAFLD is not currently available. Dr. David Garcia has an excellent foundation in lifestyle interventions that has positioned him well to advance toward his goal of reducing obesity-related disease burden in Mexican-American males. The goal of this NIMHD K01 Mentored Research Scientist Development Award is to provide Dr. Garcia with an in-depth understanding of metabolic and pathogenic pathways and risk factors of obesity-related cancers and related diseases, with a specific focus on NAFLD and HCC in Mexican-American men. He also will gain training in non-invasive imaging biomarkers (e.g., transient elastography) for the evaluation and management of disease state and risk factors. Lastly, he will advance his knowledge and skill development in research methodologies (e.g., quantitative analysis and qualitative inquiry) that informs on the design and tailoring of a culturally-specific study to reduce the burden of NAFLD. With the mentorship of Dr. Cynthia Thomson and Dr. Michael Fallon, co-mentors, and collaborators; for the proposed project Dr. Garcia intends to 1) use an available dataset from the Cameron County Hispanic Cohort (CCHC) to assess risk for NAFLD, including the influence of phenotypic factors (lifestyle behaviors) in Mexican-American men; 2) evaluate the knowledge, attitudes, and beliefs of obesity-related cancer risk, with an emphasis on NAFLD and HCC risk in Mexican-American men; and 3) assess the feasibility, acceptability, and preliminary efficacy of a NAFLD-specific weight loss intervention tailored for Mexican-American men. The training plan and research strategy in this K01 application will afford Dr. Garcia the time, resources, and mentorship necessary to achieve his career goal which is enthusiastically endorsed by University of Arizona leaders and an extremely appropriate and supportive research environment.