Abstract Non-alcoholic steatohepatitis (NASH) is quickly becoming the leading HCC etiology. NASH can lead to HCC by altering liver metabolism, inducing oncogenic mutations, causing tumor promoting inflammation as well as the immunosuppression of anti-HCC immunity. We have established an accurate model for studying NASH-induced HCC development, the MUP-uPA mouse, and used it to show that elevated TNF production by liver macrophages contributes to both NASH and HCC progression. The major cause of TNF induction during NASH is gut-derived endotoxin, whose infiltration into the portal circulation is enhanced by barrier disrupting diets that are high in fats or fructose. By disrupting autophagy and activating NF-kB, HFD feeding of MUP-uPA mice results in accumulation of p62, the major constituent of Mallory-Denk bodies, within hepatocytes. Accumulation of p62 is not required for induction of hepatosteatosis but it greatly accelerates and enhances NASH to HCC progression through the activation of NRF2 and mTORC1. Conditional activation of NRF2 in hepatocytes results in hepatomegaly due to induction of EGF and PDGF family members as well as altered liver metabolism, in part by triggering the degradation of fructose-1,6 bisphosphate phosphatase (FBP1). FBP1 is rate limiting for gluconeogenesis and its germ-line inherited deficiency results in a complex metabolic disorder that includes hypoglycemia, lactic acidosis, hepatomegaly, hepatosteatosis, hyperlipidemia and liver damage and is manifested only in response to glucose starvation. By generating Fbp1ΔHep mice, we found that FBP1 has enzymatic and non-enzymatic activities, the latter of which are due to formation of a multiprotein complex with aldolase B (ALDOB) and PP2A-C that interacts with AKT, dephosphorylates it and inhibits its activation. By inhibiting AKT activation, FBP1 and ALDOB suppress HCC development. Citation Format: Michael Karin, Li Gu, Yahui Zhu. Metabolic control of HCC initiation and progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA04.
Cognitive activities influence the rate and direction of eye movements, but the effect of various levels of eye activity on cognition has not been tested.
The interrelationship among health behaviors are not clearly understood. We examined health risk behaviors and their relationship to various types of physical activity in an ethnically diverse group of 576 men and women (mean age 24.5±2 yr) at a large urban university. Measures of risk behaviors were obtained by questionnaire, while physical activity was assessed by telephone interview using the Blair Seven Day Recall. Hierarchical multiple regressions were conducted to determine whether health risk behaviors of men and women were associated with physical activity after adjusting for potential demographic confounders, including ethnic status, marital status or employment status. Nineteen risk behavior items were factor analyzed, yielding five risk behavior factors, including tobacco use, drinking and driving, eating fatty foods, lack of healthy foods, and unsafe sex risk scales for men and for women. For men, the regression analyses demonstrated a relationship between physical activity and eating healthy foods (r=0.24, p<0.05), but no association with other risk behaviors, nor was there a relationship between demographic confounders and physical activity. For women, total energy expenditure was related to eating fewer fatty foods (r=0.15), while engaging in vigorous physical activity was associated with eating more healthy foods(r=0.14). Unmarried women were more likely to engage in physical activity than married women (r=0.13), but this finding was not present for men. In addition, European American women participated in more vigorous physical activity than did all other ethnic groups (r=0.13, p<0.01). Physical activity was not strongly related to other health behaviors in this sample of college seniors. Further examination of these relationships is needed to help health promotion professionals design interventions for specific populations.
Objective To examine the tracking (ie, the stability over time) of dietary intake in Mexican-American and white children aged 4 to 12 years. Subjects Children 4 years of age (n=351) were assessed at baseline and 65% (n=228) completed the 8-year study. Design Cardiovascular disease-related dietary intake was defined as energy, percent of energy from fat, and sodium (mg/1,000 kcal). From age 4 to 7 years, a modified 24-hour recall with observation of lunch and dinner and interview of the primary food preparer for unobserved foods was used to describe dietary intake. For children aged 11 to 12 years, a standardized 24-hour recall was used. Statistical Analyses A mixed effects model that adjusted for sex, ethnicity, and measurement wave allowed for separation of shorter-term variations in diet from more stable (“between subject”) variations. Extent of between-subject variance is an indication of tracking. Results From age 4 to age 7, there were statistically significant between-subject variance components for energy (P<.00001), percent of energy from fat (P<.00001), and sodium per 1,000 kcals (P<.001); for ages 11 and 12, energy intake was significant (P<.00001). There were no significant associations for dietary intake from age 4 to 12 years. Conclusions/Applications It seems that dietary intakes are stable over short periods and at earlier ages compared with longer intervals and later ages. Nutrition interventions are needed in childhood and throughout adolescence. J Am Diet Assoc. 2002;102:683–689.
We developed and evaluated a brief measure of fruit and vegetable consumption for adolescents. The measure was reliable and significantly correlated with 3-day food record data. Correct classification rate (63%) and specificity (63%) were good. Sensitivity (33%) was lower. The measure is recommended, although improvements in classification are still needed.
