Liver connection references

[Guest guest]

Still hounding out any possible liver connections - any comments welcome.

 

Alkaline Phosphotase levels are frequently raised in Cushings, but I don't

know if that is because of a liver effect or not yet? It is a liver enzyme,

but non-specific, ie can also indicate eg increased bone turnover.

 

It seems that in small animals the 'pot bellied' appearance in Cushings is

caused in part by an enlargement of the liver. Why?

 

If you search liver disease on vet sites you find:

 

" Fatty liver can be caused by a number of metabolic conditions such as

diabetes, Cushing's disease, protein deficiencies, hypothyroidism and more " .

 

and..

 

Metabolic diseases that cause secondary liver problems:

Hypothyroidism

Diabetes Mellitus

Pancreatitis

Hyperthyroidism

Cushing's

Inflammatory Bowel Disease

Hypoadrenocorticism

Protein-losing enteropathy

 

It can also work the other way round:

 

From (human) Merck:

 

" Hyperadrenocorticism in liver disease: In some patients with chronic liver

disease, especially associated with alcoholism, a clinical picture similar

to Cushing's syndrome may appear. Laboratory tests show a high plasma level

of cortisol, with limited diurnal variation. Cortisol secretory rates are

normal. The elevated plasma cortisol levels are partly a result of reduced

ability of the liver to oxidize cortisol to its inactive metabolite,

cortisone, but persistence of elevated plasma cortisol levels also implies

reduced sensitivity of the hypothalamic-pituitary-adrenal feedback

mechanism, which should (but does not) reduce ACTH secretion. Improvement in

liver function may correct the abnormality. "

 

Just stumbled across this too:

 

" Cortisol inhibits lymphocytic function, causing infections with pathogens

usually well tolerated (especially candida). "

 

.............

 

I did a search on oxidative stress/liver effects, and stumbled across the

following common association between insulin resistance/hyperinsulinemia,

and a fatty liver state (steatosis - which can lead to inflammation, and

eventually cell damage - steatohepatitis).

 

Interesting. It is largely asymptomatic until serious - but may in some

cases cause abdominal tenderness, fatigue, malaise, headache, tiredness,

confusion, liver enlargement.

 

Later signs include pain and anorexia/weightloss, loose stools

 

It is associated with lactic acidosis, when there is shortness of breath.

 

Cortisosteroids can induce a fattty liver state - I think this may be the

reason for enlargement seen in small animals with cushings.

 

TCM version:

 

http://www.chinesemedicaldiabetes.com/articles/articles/article_fatty_liver.

html

 

It seems to correspond with liver qi stagnation/depression/blood stasis at

first.

 

Jackie

 

 

 

Am J Med 1999 Nov;107(5):450-5

Association of nonalcoholic fatty liver disease with insulin resistance.

 

Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E,

McCullough AJ, Forlani G, Melchionda N

 

Department of Internal Medicine and Gastroenterology, Cattedra di Malattie

del Metabolismo, Universita di Bologna, Italy.

 

BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease is frequently

associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but

some patients have normal glucose tolerance or normal weight. We tested the

hypothesis that there is an association between nonalcoholic fatty liver

disease and insulin resistance that is independent of diabetes and obesity.

.......: Patients with nonalcoholic fatty liver

disease were characterized by fasting and glucose-induced hyperinsulinemia,

insulin resistance, postload hypoglycemia, and hypertriglyceridemia.........

CONCLUSION: Nonalcoholic fatty liver

disease is associated with insulin resistance and hyperinsulinemia even in

lean subjects with normal glucose tolerance. Genetic factors that reduce

insulin sensitivity and increase serum triglyceride levels may be

responsible for its development.

 

 

The liver in obesity and type 2 diabetes mellitus.

 

Li Z, Clark J, Diehl AM.

 

Division of Gastroenterology, Department of Medicine, Johns Hopkins

University School of Medicine, 912 Ross Research Building, 720 Rutland

Avenue, Baltimore, MD 21205, USA.

 

Obesity and type 2 diabetes are associated strongly with NAFLD. It is not

clear if one of these conditions causes the others, or if all are

consequences of another process. Although NAFLD is known to occur in overly

lean individuals, which indicates that excessive adiposity is not required

for the development of NAFLD, the severities of insulin resistance and NAFLD

tend to parallel each other, and the greatest prevalence of type 2 diabetes

occurs in patients with NAFLD and cirrhosis. This observation suggests that

insulin resistance and NAFLD may be related pathogenically. Experiments in

mice demonstrate that insulin resistance and NAFLD result from a chronic

inflammatory state that is characterized by increased levels of TNF alpha.

The mechanisms that drive this chronic inflammation are unknown but might

involve the oxidative stress that develops during fatty acid metabolism or

when products from intestinal bacteria escape into the mesenteric blood to

trigger a sustained hepatic inflammatory cytokine response in genetically

susceptible individuals, promoting a positive feedback loop that reinforces

insulin resistance and inflammation. This hypothesis is supported by some

animal and human studies; however, more research is needed to evaluate this

theory. Additional studies also are required to determine the benefits of

treatments that interrupt this pathogenic cascade at various points.

Preliminary work in animal and human studies suggests that diverse

strategies that inhibit production of TNF alpha and improve insulin

resistance also ameliorate NAFLD.

 

 

1: Best Pract Res Clin Gastroenterol 2002 Oct;16(5):709-31 Related Articles,

Links

 

The metabolic abnormalities associated with non-alcoholic fatty liver

disease.

 

Haque M, Sanyal AJ.

 

Division of Gastroenterology, Hepatology and Nutrition, Department of

Internal Medicine, Virginia Commonwealth University, MCV Box 980711,

Richmond, VA, 23298-0711, USA

 

Non-alcoholic fatty liver disease (NAFLD) is a common disorder in the

Western hemisphere. It encompasses two histological lesions: fatty liver and

steatohepatitis. A large body of literature indicates that insulin

resistance is a key pathophysiological abnormality in patients with NAFLD.

Insulin resistance results from a complex interplay between the major

targets of insulin action, i.e. muscle, adipose tissue and liver, versus the

ability of the pancreatic islet beta cells to compensate for insulin

resistance by increasing insulin production. The metabolic and clinical

profile associated with insulin resistance is thus defined by the factors

that produce and maintain insulin resistance and the effects of decreased

insulin sensitivity on various insulin-dependent pathways. The major

metabolic defects associated with insulin resistance are increased

peripheral lipolysis, increased hepatic glucose output due to increased

gluconeogenesis and increased lipid oxidation. This is associated with an

oxidative stress in the liver that may be compounded by additional

pathophysiological abnormalities. While much work remains to be done, the

current understanding of the pathogenesis of NAFLD provides direction for

both future investigation and development of therapeutic trials.

 

 

1: Am J Physiol Gastrointest Liver Physiol 2002 Oct;283(4):G957-64 Related

Articles, Links

 

Nonalcoholic fatty liver disease: relationship to insulin sensitivity and

oxidative stress. Treatment approaches using vitamin E, magnesium, and

betaine.

 

Patrick L.

 

Nonalcoholic steatotic hepatitis (NASH), the most prevalent form of

progressive liver disease in the United States, is considered to be a

manifestation of insulin resistance syndrome. There is increasing evidence

that steatosis in NASH is a result of the pathology in fat metabolism

occurring in obesity and insulin resistance. For steatosis to progress to

necroinflammation and fibrosis, however, the theory of mitochondrial

oxidative-stress induced cellular damage is receiving wide acceptance.

Treatment approaches that address these etiologies are reviewed: betaine,

magnesium, and vitamin E.

 

 

Article:

 

Fatty liver pathogenesis

 

A correlation between indices of insulin resistance, with or without

diabetes, and fatty liver has been well established in adults and children

in earlier studies (2, 3, 4, 5, 6, 7, 8). Why hyperinsulinemia would cause

hepatic steatosis can be explained by the known mechanisms of insulin action

(9). Insulin downregulates mitochondrial -oxidation of fatty acids in the

liver by shuttling acyl-CoA moieties toward cytosolic triglyceride

synthesis. Unfortunately, insulin may also block the secretion of

triglyceride from hepatocytes by increasing the intracellular degradation of

the very low density lipoprotein (VLDL) component, apolipoprotein B100, and

blocking exocytosis of VLDL-containing vesicles. The net result is that

hyperinsulinemia causes hepatocyte triglyceride synthesis to be increased

while its secretion as VLDL is simultaneously impaired. Insulin also plays

an important role in downregulating free fatty acid release from adipocyte

stores. As part of insulin resistance syndromes, this homeostatic mechanism

is disrupted, and peripheral fat stores continue to send free fatty acids to

the liver, even in the fed state. This increased flux of peripherally

derived fatty acids amplifies the adverse effects of insulin-mediated

defects in fatty acid disposal and further contributes to the accumulation

of triglyceride in the liver......

 

The high prevalence of hyperinsulinemia raises two important points. First,

hyperinsulinemia may be an important causative factor in the development of

NASH. However, until treatment trials directed at improving insulin

resistance are undertaken for NASH, a causative relationship cannot be

established. In fact, limited animal data suggest that conditions that

induce fatty liver also cause hyperinsulinemia (13)..........

 

An association between hyperinsulinemia and the development of the hallmarks

of nonalcoholic steatohepatitis (NASH)-specifically, steatosis,

inflammation, and cellular injury-has only recently been observed.

 

Previous epidemiological studies have indicated that NASH is likely a

heterogeneous syndrome, and the observation that not all patients exhibit

hyperinsulinemia further supports this conclusion

 

http://www-east.elsevier.com/ajg/issues/9610/ajg4571edi.htm

 

 

 

1: Cell Biochem Funct 2002 Dec;20(4):297-302 Related Articles, Links

 

 

Effects of cod liver oil on tissue antioxidant pathways in normal and

streptozotocin-diabetic rats.

 

Hunkar T, Aktan F, Ceylan A, Karasu C.

 

Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara,

Turkey.

 

Lipid disorders and increased oxidative stress may exacerbate some

complications of diabetes mellitus. Previous studies have implicated the

beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids

(PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the

protection of cells from the destructive effect of increased lipids and

lipid peroxidation products. This study, therefore, was designed to

investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which

comprises mainly vitamin A, PUFAs, EPA and DHA. ....... The current study

suggests that the treatment of diabetic rats with CLO provides better

control of

glucose and lipid metabolism, allows recovery of normal growth rate,

prevents oxidative/peroxidative stress and ameliorates endogenous

antioxidant enzyme activities in various tissues. Because CLO contains a

plethora of beneficial compounds together, its use for the management of

diabetes-induced complications may provide important advantages. Copyright

2002 John Wiley & Sons, Ltd.

 

 

1: Br J Nutr 2003 Jan;89(1):11-8 Related Articles, Links

 

Effects of fish oil- and olive oil-rich diets on iron metabolism and

oxidative stress in the rat.

 

Miret S, Saiz MP, Mitjavila MT.

 

Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona,

Avda. Diagonal, 645, Spain.

 

The objective of the present study was to examine the effects of fish oil

(FO)- and olive oil (OO)-rich diets on Fe metabolism and oxidative stress.

Rats were fed for 16 weeks with diets containing 50 g lipids/kg; either OO,

maize oil (MO) or FO. OO or MO diets contained a standard amount (100 mg/kg)

of all-rac-alpha-tocopheryl acetate. FO diets were supplemented with 0, 100

or 200 mg all-rac-alpha-tocopheryl acetate/kg (FO-0, FO-1 or FO-2 diets,

respectively). At the end of the feeding period, we measured non-haem Fe

stores in liver and spleen, and erythrocyte and reticulocyte count. We also

determined antioxidants and products derived from lipid peroxidation in

plasma and erythrocytes. Our results showed reduced non-haem Fe stores in

rats fed any of the FO diets. Reticulocyte percentage was higher in the rats

fed FO-0 and FO-1. Plasma alpha-tocopherol was very low in rats fed the FO-0

diet. Rats fed the FO-1 and FO-2 diets showed higher alpha-tocopherol in

plasma than the FO-0 group but lower than the MO or OO groups. We did not

observe such differences in the alpha-tocopherol content in erythrocyte

membranes. Superoxide dismutase and glutathione peroxidase activities were

lower in the erythrocytes of rats fed the FO-0 diet. The products derived

from lipid peroxidation were also higher in the FO groups. The

administration of FO-rich diets increased lipid peroxidation and affected Fe

metabolism. On the other hand, the OO-rich diet did not increase oxidative

stress

 

............

 

" Choline and Inositol, are B vitamins which act as lipotropic agents to aid

in the prevention of fat accumulation in the liver (9). Like biotin, choline

plays a rate limiting role in the removal of fatty acids from the liver. If

choline is deficient, a fatty liver can result which leaves the horse with

higher concentrations of triglycerides in the liver and a reduction in the

release of lipoproteins into the blood. Instol helps to properly utilize

choline and promotes healthy hair, hoof, and bone. "

 

Jackie