High-Fructose/High-Fat Diet Downregulates the Hepatic Mitochondrial Oxidative Phosphorylation Pathway in Mice Compared with High-Fat Diet Alone.

Both high-fat diet (HFD) alone and high-fructose plus HFD (HFr/HFD) cause diet-induced non-alcoholic fatty liver disease in murine models. However, the mechanisms underlying their impacts on inducing different levels of liver injury are yet to be elucidated. This study employed a proteomic approach to elucidate further on this issue. Adult male C57BL/6J mice were allocated to the HFD or the HFr/HFD group. After feeding for 12 weeks, all mice were euthanized and samples were collected. The proteomic profiles in liver tissues were analyzed using liquid chromatography-tandem mass spectrometry followed by canonical pathway analysis. We demonstrated that the mitochondrial oxidative phosphorylation (OXPHOS) pathway was the most significantly downregulated canonical pathway in the HFr/HFD group when compared with the HFD group. Within the OXPHOS pathway, the HFr/HFD group demonstrated significant downregulation of complexes I and III and significant upregulation of complex IV when compared with the HFD group. Moreover, the HFr/HFD group had lower protein levels of NADH: ubiquinone oxidoreductase subunits S3, S6, A5, and A12 in complex I (p < 0.001, =0.03, <0.001, and <0.001, respectively), lower protein level of cytochrome C in complex III (p < 0.001), and higher protein level of cytochrome C oxidase subunit 2 in complex IV (p = 0.002), when compared with the HFD group. To summarize, we have demonstrated that the hepatic mitochondrial OXPHOS pathway is significantly downregulated in long-term HFr/HFD feeding when compared with long-term HFD feeding. These data support the concept that the hepatic mitochondrial OXPHOS pathway should be involved in mediating the effects of HFr/HFD on inducing more severe liver injury than HFD alone.

Fatigue following type 2 diabetes: Psychometric testing of the Indonesian version of the multidimensional fatigue Inventory-20 and unmet fatigue-related needs.

Patients with type 2 diabetes mellitus (T2DM) often experience fatigue. The Multidimensional Fatigue Inventory (MFI-20) is a valid tool for evaluating fatigue; however, its psychometric properties have not been examined in Indonesian-speaking patients with T2DM. This study assessed the psychometric properties of the Indonesian version of the Multidimensional Fatigue Inventory-20 (IMFI-20) in patients with T2DM and investigated fatigue in a health-care setting. A cross-sectional design was adopted. Two hundred patients with T2DM were interviewed in clinics. Five self-structured measures were used to assess the frequency and duration of fatigue and the health-care utilization of patients with fatigue. Cronbach's alpha and intraclass correlation (ICC) were used to evaluate the internal consistency and test-retest reliability of the Indonesian version of the MFI-20 (IMFI-20). The criterion, convergent, and known-group validity of the IMFI-20 were also examined, and its underlying structure was determined using explanatory factor analysis. The STROBE checklist was used. The results revealed that approximately half of the patients experienced fatigue. Among those with fatigue, 62% reported that their fatigue was rarely or never treated by their physicians. The IMFI-20 exhibited satisfactory model fit, excellent internal consistency (Cronbach's alpha of 0.92), and test-retest ICC of 0.93. The IMFI-20 was significantly associated with the Functional Assessment of Chronic Illness Therapy-Fatigue, Beck Depression Inventory-Second Edition, and Pittsburgh Sleep Quality Index (r = 0.705, 0.670, and 0.581, respectively). The IMFI-20 exhibited known-group validity for unfavorable sleep quality and HbA1C ≥ 6.5%. Our findings suggest that patients with T2DM who experience fatigue are often overlooked by health-care providers, and that the IMFI-20, which exhibits excellent psychometric properties, can be adopted by studies that use fatigue as an endpoint in Indonesian-speaking populations.