Aaron Justin Yeoh

All Publications

• The Reply. The American journal of medicine Yeoh, A., Wong, R. J. 2024; 137 (7): e143

  View details for DOI 10.1016/j.amjmed.2024.03.027

  View details for PubMedID 38942497

• A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease. Hepatology international Zhang, H., Targher, G., Byrne, C. D., Kim, S. U., Wong, V. W., Valenti, L., Glickman, M., Ponce, J., Mantzoros, C. S., Crespo, J., Gronbaek, H., Yang, W., Eslam, M., Wong, R. J., Machado, M. V., Yu, M. L., Ghanem, O. M., Okanoue, T., Liu, J. F., Lee, Y. H., Xu, X. Y., Pan, Q., Sui, M., Lonardo, A., Yilmaz, Y., Zhu, L. Y., Moreno, C., Miele, L., Lupsor-Platon, M., Zhao, L., LaMasters, T. L., Gish, R. G., Zhang, H., Nedelcu, M., Chan, W. K., Xia, M. F., Bril, F., Shi, J. P., Datz, C., Romeo, S., Sun, J., Liu, D., Sookoian, S., Mao, Y. M., Méndez-Sánchez, N., Wang, X. Y., Pyrsopoulos, N. T., Fan, J. G., Fouad, Y., Sun, D. Q., Giannini, C., Chai, J., Xia, Z. F., Jun, D. W., Li, G. J., Treeprasertsuk, S., Li, Y. X., Cheung, T. T., Zhang, F., Goh, G. B., Furuhashi, M., Seto, W. K., Huang, H., Di Sessa, A., Li, Q. H., Cholongitas, E., Zhang, L., Silveira, T. R., Sebastiani, G., Adams, L. A., Chen, W., Qi, X., Rankovic, I., De Ledinghen, V., Lv, W. J., Hamaguchi, M., Kassir, R., Müller-Wieland, D., Romero-Gomez, M., Xu, Y., Xu, Y. C., Chen, S. Y., Kermansaravi, M., Kuchay, M. S., Lefere, S., Parmar, C., Lip, G. Y., Liu, C. J., Åberg, F., Lau, G., George, J., Sarin, S. K., Zhou, J. Y., Zheng, M. H. 2024

  Abstract

  With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

  View details for DOI 10.1007/s12072-024-10702-5

  View details for PubMedID 38878111

  View details for PubMedCentralID 7309235

• Impact of Human Immunodeficiency Virus Infection on Liver and Cardiovascular Outcomes in Veterans with Metabolic Dysfunction Associated Steatotic Liver Disease. The American journal of gastroenterology Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. 2024

  Abstract

  Hepatic steatosis in highly prevalent in people living with human immunodeficiency virus (HIV). It remains unclear whether HIV in patients with metabolic dysfunction associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among U.S. Veterans with MASLD.Using national Veterans Administration data from 2010-2022, we created a propensity score matched cohort of MASLD patients with vs. without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs. without HIV as well as MASLD-HIV patients on anti-retroviral therapy (ART) vs. not on ART. Secondary outcomes included incidence of major adverse cardiovascular events (MACE) and overall survival.The propensity matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and were similar in demographics and co-morbidities. Compared to MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared to MASLD patients without HIV, incidence of MACE was higher among MASLD patients with HIV (5.18 vs. 4.48 per 100 person-years, p=0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART.Among U.S. Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed.

  View details for DOI 10.14309/ajg.0000000000002760

  View details for PubMedID 38477465

• Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among U.S. Veterans with Steatotic Liver Disease. Gastroenterology Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. 2024

  Abstract

  BACKGROUND & AIMS: Conflicting data exists on impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aim to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among Veterans with steatotic liver disease.METHODS: U.S. Veterans with steatotic liver disease were identified from January 2010 to December 2022. Alcohol use was assessed using documented AUDIT-C scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), high-risk alcohol (AUDIT-C > 3 for women and > 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow up.RESULTS: 1,156,189 Veterans with steatotic liver disease were identified (54.2% no alcohol, 34.6% low-risk alcohol, 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have 43% higher incidence of cirrhosis compared to patients reporting no alcohol use. Compared to patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow up experienced a 39% reduction in long-term risk of cirrhosis (HR 0.61, 95% CI 0.45-0.83, p< 0.01).CONCLUSIONS: One in nine Veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared to no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

  View details for DOI 10.1053/j.gastro.2024.02.032

  View details for PubMedID 38428619

• The Reply. The American journal of medicine Yeoh, A., Cheung, R., Ahmed, A., Chitnis, A. S., Do, A., Wong, R. J. 2024; 137 (1): e15

  View details for DOI 10.1016/j.amjmed.2023.08.024

  View details for PubMedID 38061829

• EXPOSURE TO GLP1RA THERAPY IS ASSOCIATED WITH IMPROVED SURVIVAL IN POST LIVER TRANSPLANT PATIENTS WITH TYPE I I DIABETES MELLITUS Achalu, S., Berry, R., Manikat, R., Yeoh, A., Gombar, S., Kim, S. H., Ghaziani, T., Dronamraju, D., Dhanasekaran, R., Kwong, A. J., Torok, N. J., Goel, A., Kim, W., Kwo, P. LIPPINCOTT WILLIAMS & WILKINS. 2023: S311-S312

  View details for Web of Science ID 001094865400315

• High-Risk Alcohol Use Is Associated With Significantly Greater Risk of Incident Hepatocellular Carcinoma in a National Cohort of US Veterans With Metabolic Dysfunction Associated Fatty Liver Disease Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1043

  View details for Web of Science ID 001091849303063

• Evaluating the Association Between Concurrent Human Immunodeficiency Virus Infection and Risk of Cardiovascular Disease in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1043-S1044

  View details for Web of Science ID 001091849303064

• CONCURRENT HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN PATIENTS WITH METABOLIC DYSFUNCTION ASSOCIATED FATTY LIVER DISEASE IS ASSOCIATED WITH SIGNIFICANTLY GREATER RISKS OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA Wong, R. J., Yang, Z., Yeoh, A., Do, A., Ahmed, A., Cheung, R. LIPPINCOTT WILLIAMS & WILKINS. 2023: S935-S936

  View details for Web of Science ID 001094865402123

• THE ASSOCIATION BETWEEN BASELINE ALCOHOL USE AND LONG-TERM RISK OF INCIDENT CIRRHOSIS AMONG A NATIONAL COHORT OF US VETERANS WITH METABOLIC DYSFUNCTION ASSOCIATED FATTY LIVER DISEASE Wong, R. J., Yang, Z., Cheung, R., Singal, A. K., Do, A., Ahmed, A., Yeoh, A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1045-S1046

  View details for Web of Science ID 001094865402225

• Incidence of Cirrhosis and Hepatocellular Carcinoma Among Veterans With Noncirrhotic Metabolic Dysfunction-associated Fatty Liver Disease. Journal of clinical gastroenterology Yeoh, A., Yang, Z., Cheung, R., Do, A., Ahmed, A., Wong, R. J. 2023

  Abstract

  BACKGROUND AND AIMS: Despite the high prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), the long-term incidence of cirrhosis or hepatocellular carcinoma (HCC) among adults with MAFLD is not well described. Using a national cohort of United States Veterans, we evaluated the overall incidence and predictors of cirrhosis and HCC among adults with noncirrhotic MAFLD.METHODS: Data from the 2010 to 2022 Veterans Affairs database were used to identify adults with noncirrhotic MAFLD using established definitions. Five and 10-year incidence of cirrhosis and HCC were assessed and stratified by demographics and relevant clinical variables. Multivariate Cox proportional hazard models were utilized to determine predictors of cirrhosis and HCC.RESULTS: Among 969,253 patients with noncirrhotic MAFLD (94.5% males, 70.2% non-Hispanic white, mean age of 62.7 ± 12.2 y), the 10-year incidence of cirrhosis and HCC was 3.70% (95% CI: 3.66-3.74) and 0.69% (95% CI: 0.67-0.70), respectively. When stratified by race/ethnicity, the 10-year incidence of cirrhosis was lowest among Asians (2.63%, 95% CI: 2.37-2.88) and highest among Hispanics (4.60%, 95% CI: 4.45-4.75), a pattern also observed with HCC. Significant disparities in risk of cirrhosis or HCC were observed when stratified by sex, substance use, and comorbidities. Risks of cirrhosis and HCC were highest in patients with baseline fibrosis-4 >2.67.CONCLUSION: This large study provides important epidemiological data describing the natural history of adults with MAFLD. Disparities in risk of cirrhosis and HCC were observed by demographic and clinical characteristics, emphasizing the importance of early identification of MAFLD with modifiable high-risk features to implement earlier interventions to improve long-term outcomes.

  View details for DOI 10.1097/MCG.0000000000001921

  View details for PubMedID 37678412

• Tacrolimus-Induced Esophageal and Colon Ulcers ACG CASE REPORTS JOURNAL Vazquez-Reyes, R., Yeoh, A., Kamal, A. 2023; 10 (6)

  View details for DOI 10.14309/crj.0000000000001072

  View details for Web of Science ID 001001976900001

• Severe Diarrhea and Weight Loss Due to Protein-Losing Enteropathy: Don't Pass Up the PAS Stain. Digestive diseases and sciences Yeoh, A., Kulkarni, C., Ryan, E., Berry, G., Triadafilopoulos, G. 2023

  View details for DOI 10.1007/s10620-023-07982-6

  View details for PubMedID 37231192

• The Role Bariatric Surgery and Endobariatric Therapies in Nonalcoholic Steatohepatitis. Clinics in liver disease Yeoh, A., Wong, R., Singal, A. K. 2023; 27 (2): 413-427

  Abstract

  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Disease spectrum varies from steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, there are no approved medical therapies, and weight loss through lifestyle modifications remains a mainstay of therapy. Bariatric surgery is the most effective therapy for weight loss and has been shown to improve liver histology. Recently, endoscopic bariatric metabolic therapies have also emerged as effective treatments for patients with obesity and NAFLD. This review summarizes the role of bariatric surgery and endoscopic therapies in the management of patients with NAFLD.

  View details for DOI 10.1016/j.cld.2023.01.009

  View details for PubMedID 37024216

• Cardiovascular Disease Risk and Statin Use Among Adults with Metabolic Dysfunction Associated Fatty Liver Disease. The American journal of medicine Yeoh, A., Cheung, R., Ahmed, A., Chitnis, A. S., Do, A., Wong, R. J. 2023

  Abstract

  BACKGROUND: A leading cause of mortality in fatty liver disease is cardiovascular disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is new terminology that classifies fatty liver due to metabolic dysfunction attributable to obesity and associated complications. We evaluated atherosclerotic cardiovascular disease (ASCVD) risk and statin use in adults with MAFLD.METHODS: Retrospective study of 2011-2018 National Health and Nutrition Examination Survey. Adults with MAFLD were identified using established criteria: presence of hepatic steatosis (US Fatty Liver Index>30) plus ≥1 of the following: (1) body mass index >25 kg/m2 in non-Asians or >23 kg/m2 in Asians, (2) diabetes mellitus, or (3) ≥2 metabolic risk factors. cardiovascular disease risk was estimated using the validated 10-year ASCVD risk score. Statin use was assessed in intermediate and high 10-year ASCVD risk groups.RESULTS: Prevalence of MAFLD was 34.8% (95% CI 33.9%-35.8%), comprising 54.4% men, 27.9% age ≥65y, and 38.2% non-Hispanic white. Among adults with MAFLD, 23.3% and 23.0% had intermediate and high 10-year ASCVD risk, respectively. Compared to women, men were more likely to have high 10-year ASCVD risk (28.7% vs. 16.1%, adjusted OR (aOR) 5.24, 95% CI 3.87-7.10, p<0.01). In intermediate and high ASCVD risk groups, overall statin use was 48.3% (95% CI 46.1-51.3).CONCLUSIONS: Over 46% of adults with MAFLD had intermediate or high 10-year ASCVD risk. Statin use was underutilized at 48.3% in those meeting statin criteria. These findings are alarming given high cardiovascular disease risk and low statin use in this cohort.

  View details for DOI 10.1016/j.amjmed.2023.03.010

  View details for PubMedID 37001720

• Racial/Ethnic Disparities in Long-Term Risks of Cirrhosis Among US Veterans With Metabolic Dysfunction-Associated Fatty Liver Disease Yeoh, A. J., Yang, Z., Cheung, R., Wong, R. LIPPINCOTT WILLIAMS & WILKINS. 2022: S869-S870

  View details for Web of Science ID 000897916003034

• Tacrolimus-Induced Esophageal and Colon Ulcers: A Case Report Vazquez-Reyes, R., Yeoh, A. J., Kamal, A. N. LIPPINCOTT WILLIAMS & WILKINS. 2022: S1697-S1698

  View details for Web of Science ID 000897916005497

• Cost-effectiveness of earlier or more intensive colorectal cancer screening in overweight and obese patients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Yeoh, A., Mannalithara, A., Ladabaum, U. 2022

  Abstract

  Overweight and obese persons have elevated rates of colorectal cancer (CRC) but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons.We adapted our validated decision analytic model of CRC screening to compare screening starting at age 45 or 40 instead of 50, and/or shortening screening intervals, in women and men with body-mass-index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 (Colo10) or 5 years (Colo5), or annual FIT.Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I-III, reflecting the counterbalancing of higher CRC risk by lower life-expectancy as BMI rises. For all BMI/sex groups, Colo10 starting at 45 or FIT starting at 40 were cost-effective at a threshold of $100,000/quality-adjusted life year (QALY) gained. Colo10 starting at 40 was cost-effective only for men with obesity II-III, at $93,300 and $80,400/QALY gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks.CRC screening starting at age 45 with colonoscopy, or 40 with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II-III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening.

  View details for DOI 10.1016/j.cgh.2022.07.028

  View details for PubMedID 35940514

• Single Intact Pill Causing Biliary Stent Obstruction. ACG case reports journal Yeoh, A., Ryou, M. 2019; 6 (8): e00196

  View details for DOI 10.14309/crj.0000000000000196

  View details for PubMedID 31737726

  View details for PubMedCentralID PMC6791609

• Visual Processing Impairments Detected by Oculometric Assessment Provide Evidence of Obesity-Related Neurological Dysfunction Yeoh, A., Wong, K., Liston, D., Papademetriou, S., Okafor, P. N. NATURE PUBLISHING GROUP. 2018: S586–S587

  View details for Web of Science ID 000464611002157

• Reproducibility of a novel computed-tomography based measurement of renal papillary density in the Framingham Heart Study. BMC research notes Yeoh, A. J., Massaro, J., Fox, C. S., Hoffmann, U., Eisner, B. H., McMahon, G. M. 2015; 8: 811-?

  Abstract

  Renal papillary calcification is a compelling candidate risk factor for chronic kidney disease (CKD) and nephrolithiasis. Renal papillary density (RPD), as assessed by computed tomography (CT), is a potential marker for calcification that has not been well studied. We developed a protocol to measure RPD using CT scans and assessed its reproducibility in participants from the Framingham Heart Study.We assessed RPD of right kidneys from a single abdominal CT slice in 100 representative participants from the Framingham Heart Study (47% female, mean age 59.9 years) using a novel protocol. We selected the kidney slice with the most open sinus space and assessed RPD using the average of three 20 mm(2) ellipses from upper, middle and lower papillary regions. Two different readers performed RPD measurements and the first reader repeated all measurements to determine both intra- and inter-reader reproducibility, respectively.Of 100 total individuals included in the replication dataset, six were excluded for poor scan quality. Average RPD across all individuals was 48.7 ± 4.7 (range 38.7-61.7) Hounsfield Units (HU). The intra- and inter-reader correlation coefficients were 0.86 and 0.79, respectively. Bland-Altman analysis suggested no systematic bias between the different reads.Measuring RPD is practical and reproducible using MDCT scans from a small sample of a community-based cohort.

  View details for DOI 10.1186/s13104-015-1784-6

  View details for PubMedID 26695484

  View details for PubMedCentralID PMC4688991

• The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Yeoh, A. J., Pedley, A., Rosenquist, K. J., Hoffmann, U., Fox, C. S. 2015; 100 (8): E1056-E1064

  Abstract

  Alterations in the cellular characteristics of subcutaneous adipose tissue (SAT) may reduce its ability to expand in times of caloric excess, increasing the propensity to store excess calories viscerally (visceral adipose tissue [VAT]). We hypothesized (1) that increased SAT density, an indirect marker of fat quality, would be associated with an increased VAT/SAT ratio and increased cardiovascular disease (CVD) risk and (2) that these associations would be independent of the absolute volume of SAT.We investigated the association of SAT density with the VAT/SAT ratio and CVD risk in 3212 participants (48% women, mean age, 50.7 years) from the Framingham Heart Study. Adipose tissue depot density and volume were quantified by computed tomography; traditional CVD risk factors were quantified.Higher SAT density was correlated with a higher VAT/SAT ratio in men (r = 0.17; P < .0001) but not in women (r = 0.04; P ≥ .05). More adverse levels of CVD risk factors were observed in the high SAT density/high VAT/SAT ratio group than in the referent group (low density/low ratio). For example, women had an increased risk of diabetes (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.6-17.6; P = .0001) and hypertension (OR, 1.6; 95% CI, 1.1-2.4; P = .009). Additional adjustment for SAT volume generally strengthened these associations (diabetes OR, 10.8; 95% CI, 4.1-29.0; hypertension OR, 2.5; 95% CI, 1.7-3.7; all P < .0001). These trends were similar but generally weaker in men.High fat density, an indirect marker of fat quality, is associated with the propensity to store fat viscerally vs subcutaneously and is jointly characterized by an increased burden of CVD risk factors.

  View details for DOI 10.1210/jc.2014-4032

  View details for Web of Science ID 000364855900006

  View details for PubMedID 26062015

  View details for PubMedCentralID PMC4525002

• H2A.Z-Dependent Regulation of Cohesin Dynamics on Chromosome Arms MOLECULAR AND CELLULAR BIOLOGY Tapia-Alveal, C., Lin, S., Yeoh, A., Jabado, O. J., O'Connell, M. J. 2014; 34 (11): 2092-2104

  Abstract

  Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are major determinants of chromosome structure and dynamics. The cohesin complex embraces sister chromatids throughout interphase, but during mitosis most cohesin is stripped from chromosome arms by early prophase, while the remaining cohesin at kinetochores is cleaved at anaphase. This two-step removal of cohesin is required for sister chromatids to separate. The cohesin-related Smc5/6 complex has been studied mostly as a determinant of DNA repair via homologous recombination. However, chromosome segregation fails in Smc5/6 null mutants or cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs in the fission yeast Schizosaccharomyces pombe following genotoxic and replication stress, or topoisomerase II dysfunction, and these mitotic defects are due to the postanaphase retention of cohesin on chromosome arms. Here we show that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe. Further, we identified the histone variant H2A.Z as a critical factor to modulate cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome integrity through accurate chromosome segregation.

  View details for DOI 10.1128/MCB.00193-14

  View details for Web of Science ID 000335967100015

  View details for PubMedID 24687850

  View details for PubMedCentralID PMC4019066

• Effect of body size on expression of Manduca sexta midgut genes. Journal of experimental zoology. Part A, Ecological genetics and physiology Yeoh, A. J., Davis, K., Vela-Mendoza, A. V., Hartlaub, B. A., Gillen, C. M. 2012; 317 (3): 141-151

  Abstract

  Isometric growth of larval insect midgut predicts that the ratio of midgut surface area to body mass decreases as larvae grow. Gut tissue and gut content masses were measured in first through fifth instar Manduca sexta larvae. Wet mass of gut tissue increased in relationship to body mass with a scaling exponent of 0.85 compared to an exponent of 1.33 for gut content mass, suggesting that surface area becomes increasingly limiting in larger larvae. To test the hypothesis that compensation for the decrease in relative surface area of the midgut occurs by increased expression of membrane proteins, we compared midgut mRNA expression in fourth and fifth instar. Surveyed genes encoded apical membrane proteins with diverse functions, including the potassium amino acid transporter KAAT1, ion channel CAATCH1, aminopeptidase msAPN3, V-type H-ATPase E subunit, and cation chloride cotransporter masBSC. KAAT1 was expressed 300- to 1500-fold higher in middle and posterior midgut compared to anterior midgut. Expression of msAPN3 was approximately 200-fold higher in posterior midgut than middle midgut. Expression of KAAT1 was 2.3- to 3.1-fold higher in fifth compared to fourth-instar larvae, and masBSC expression was 1.3- to 1.9-fold higher in fifth-instar larvae. Expression of msAPN3 and V-ATPase, but not KAAT1, decreased as body mass increased within the fifth instar. Although the increased expression of KAAT1 and masBSC in fifth-instar larvae supports the hypothesis of increased membrane protein expression in larger larvae, results from the other genes do not support this hypothesis.

  View details for DOI 10.1002/jez.1001

  View details for PubMedID 22311716