Effects of high-fat diet on liver injury after small bowel resection

Effective therapies are limited for patients with parenteral nutrition-dependent short bowel syndrome. We previously showed that intestinal expression of the transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7 ( tis7) is markedly increased during the adaptive response following massive small bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we further explore the functional implications of tis7 deletion in intestinal lipid metabolism and the adaptive response following small bowel resection. Intestinal tis7 transgenic ( tis7tg), tis7−/−, and wild-type (WT) littermates were subjected to 50% small bowel resection. Mice were fed a control or a high-saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery, lipid absorption, mucosal lipid analysis, and the morphometric adaptive response were analyzed. Quantitative real-time PCR was performed to identify tis7 downstream gene targets. Postresection survival was markedly reduced in high-fat, but not control, diet-fed tis7−/− mice. Decreased survival was associated with anastomotic inflammation and intestinal obstruction postresection. High-fat, but not control, diet-fed tis7−/− mice had increased intestinal IL-6 expression. Intestinal lipid trafficking was altered in tis7−/− compared with WT mice postresection. In contrast, high-fat diet-fed tis7tg mice had improved survival postresection compared with WT littermates. High-fat diet feeding in the setting of tis7 deletion resulted in postresection anastomotic inflammation and small bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may require tis7 and its target genes. The presence of luminal fat in the setting of tis7 deletion promotes an intestinal inflammatory response postresection.

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The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats

Scientific Reports ◽

10.1038/s41598-021-92510-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neesha S. Patel ◽

Ujwal R. Yanala ◽

Shruthishree Aravind ◽

Roger D. Reidelberger ◽

Jon S. Thompson ◽

...

Keyword(s):

Body Weight ◽

Small Bowel ◽

Lean Mass ◽

Bowel Resection ◽

Small Bowel Resection ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Massive Resection ◽

Obese Rats

AbstractIn patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats. Rats (CD IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored. Preoperative body weight was 884 ± 95 versus 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 versus 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% versus 5% decrease in high-fat versus low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups. The high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

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The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats

10.1101/2020.11.11.377945 ◽

2020 ◽

Author(s):

Neesha S. Patel ◽

Ujwal R. Yanala ◽

Shruthishree Aravind ◽

Roger D. Reidelberger ◽

Jon S. Thompson ◽

...

Keyword(s):

Body Weight ◽

Small Bowel ◽

Lean Mass ◽

Bowel Resection ◽

Small Bowel Resection ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Massive Resection ◽

Obese Rats

AbstractBackgroundIn patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats.MethodsRats (CD®IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored.ResultsPreoperative body weight was 884 ± 95 vs. 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 vs. 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% vs. 5% decrease in high-fat vs. low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups.ConclusionThe high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

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Liver injury after small bowel resection is prevented in obesity-resistant 129S1/SvImJ mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00284.2020 ◽

2021 ◽

Author(s):

Emily Jean Onufer ◽

Yong-Hyun Han ◽

Cathleen M. Courtney ◽

Allie E. Steinberger ◽

Maria E Tecos ◽

...

Keyword(s):

Fatty Acids ◽

Small Bowel ◽

Liver Injury ◽

Free Fatty Acids ◽

Short Bowel Syndrome ◽

Bowel Resection ◽

Small Bowel Resection ◽

Resistant Mouse ◽

Short Bowel ◽

Inflammatory Pathways

Background Intestinal failure-associated liver disease is a major morbidity associated with short bowel syndrome. We sought to determine if the obesity-resistant mouse strain (129S1/SvImJ) conferred protection from liver injury after small bowel resection (SBR). Methods Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6J and 129S1/SvImJ mice underwent a 50% proximal SBR or sham operation. At post-operative week 10, hepatic steatosis, fibrosis, and cholestasis were assessed. Hepatic and systemic inflammatory pathways were evaluated using oxidative markers and abundance of tissue macrophages. Potential mechanisms of endotoxin-resistance were also explored. Results Serum lipid levels were elevated in all mouse lines. Hepatic triglyceride levels were no different between mouse strains, but there was an increased accumulation of free fatty acids in the C57BL/6J mice. Histologic and serum markers of hepatic fibrosis, steatosis, and cholestasis were significantly elevated in C57BL/6J SBR mice as well as oxidative stress markers and macrophage recruitment in both the liver and visceral white fat in C57BL/6J resected mice compared to sham controls and the 129S1/SvImJ mouse line. Serum endotoxin levels were significantly elevated in C57BL/6J mice with significant elevation of hepatic TLR4 and reduction in PPARa expression levels. Conclusions Despite high levels of serum lipids, 129S1/SvImJ mice do not develop liver inflammation, fibrosis, or cholestasis after SBR, unlike C57BL/6J mice. These data suggest that the accumulation of hepatic free fatty acids as well as increased endotoxin-driven inflammatory pathways through PPARa and TLR4 contribute to the liver injury seen in C57BL/6J mice with short bowel syndrome.

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Relation of Small Bowel Resection to Nutrition in Man

Gastroenterology ◽

10.1016/s0016-5085(60)80035-2 ◽

1960 ◽

Vol 38 (4) ◽

pp. 605-615 ◽

Cited By ~ 36

Author(s):

M.H. Kalser ◽

J.L.A. Roth ◽

H. Tumen ◽

T.A. Johnson

Keyword(s):

Small Bowel ◽

Bowel Resection ◽

Small Bowel Resection

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Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat

European Journal of Clinical Investigation ◽

10.1111/j.1365-2362.1979.tb01677.x ◽

1979 ◽

Vol 9 (2) ◽

pp. 115-127 ◽

Cited By ~ 26

Author(s):

BRYCE TAYLOR ◽

GERARD M. MURPHY ◽

R. HERMON DOWLING

Keyword(s):

Small Bowel ◽

Bowel Resection ◽

Intestinal Adaptation ◽

Small Bowel Resection ◽

Pituitary Hormones

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Pathophysiological correlates of two unique renal tubule lesions in rats with intestinal resection

AJP Renal Physiology ◽

10.1152/ajprenal.00033.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. F1061-F1069 ◽

Cited By ~ 7

Author(s):

Elaine Worcester ◽

Andrew Evan ◽

Sharon Bledsoe ◽

Mark Lyon ◽

Mark Chuang ◽

...

Keyword(s):

Calcium Phosphate ◽

Small Bowel ◽

Bowel Resection ◽

Cell Damage ◽

Intestinal Resection ◽

Small Bowel Resection ◽

Renal Tissue ◽

Apical Surface ◽

Crystal Deposition ◽

Oxalate Excretion

Rats with small bowel resection fed a high-oxalate diet develop extensive deposition of calcium oxalate (CaOx) and calcium phosphate crystals in the kidney after 4 mo. To explore the earliest sites of renal crystal deposition, rats received either small bowel resection or transection and were then fed either standard chow or a high-oxalate diet; perfusion-fixed renal tissue from five rats in each group was examined by light microscopy at 2, 4, 8, and 12 wk. Rats fed the high-oxalate diet developed birefringent microcrystals at the brush border of proximal tubule cells, with or without cell damage; the lesion was most common in rats with both resection and a high-oxalate diet (10/19 with the lesion) and was significantly correlated with urine oxalate excretion ( P < 0.001). Rats with bowel resection fed normal chow had mild hyperoxaluria but high urine CaOx supersaturation; four of these rats developed birefringent crystal deposition with tubule plugging in inner medullary collecting ducts (IMCD). Two rats fed a high-oxalate diet also developed this lesion, which was correlated with CaOx supersaturation, but not oxalate excretion. Tissue was examined under oil immersion, and tiny birefringent crystals were noted on the apical surface of IMCD cells only in animals with IMCD crystal plugging. In one animal, IMCD crystals were both birefringent and nonbirefringent, suggesting a mix of CaOx and calcium phosphate. Overall, these animals demonstrate two distinct sites and mechanisms of renal crystal deposition and may help elucidate renal lesions seen in humans with enteric hyperoxaluria and stones.

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