Corticotropin-releasing hormone (CRH) is released from the hypothalamus, which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). Peripheral oxytocin administration reduces ethanol consumption in rats. Alcohol and Alcoholism 39(4):281286, 2004. Excessive drinking can damage an adolescent's short-term and long-term memory. ; Ribeiro, M.O. A):S10S17, 2004. At birth, plasma IGF-1 levels are at 50 percent of the adult levels and gradually increase throughout childhood with a spike during puberty, when IGF-1 plays a critical role in reproductive-organ maturation and long-bone growth. ; Hjollund, N.H.; Henriksen, T.B. A prospective population-based study of alcohol use and non-insulin-dependent diabetes mellitus. PMID: 7199834, Dearth, R.K.; Hiney, J.K.; and Dees, W.L. 2013). Reactive Oxygen Species: Biologically active, partially reduced derivatives of molecular oxygen that are produced by normal metabolic processes and which can damage the cells or their components. These effects of alcohol exposure on GH were associated with a decrease in circulating IGF-1, which could explain the growth impairments observed in animals exposed to alcohol (Srivastava et al. Many of the risks related to underage drinking are tied directly to the brain and its function. Journal of Adolescent Health Care 7(1):2833, 1986. It is responsible for making hormones that affect many body functions. ):231S237S, 1998. ; and Nyomba, B.L. Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Emanuele, N.V.; LaPaglia, N.; Steiner, J.; et al. 2010). The .gov means its official. ; et al. Adams, M.L. PMID: 20238396. 1998). The enteroinsular axis and endocrine pancreatic function in chronic alcohol consumers: Evidence for early beta-cell hypofunction. ; Stanley, D.A. Kathleen Esposito is a certified addictions counselor in the Pacific Northwest. It's the unsteady, staggering walk of a long-term alcoholic. 2004), whereas chronic exposure induces an increase in the production of proinflammatory cytokines, such as TNF (Mandrekar et al. Learn more about the passive diffusion of alcohol through the blood brain barrier. Studies found that heavy alcohol consumption results in reduced testosterone Inhibit glucose production while alcohol is being metabolized. Glycogen: A large, highly branched molecule consisting of chains of glucose molecules; constitutes the major carbohydrate reserve of animals and is stored primarily in liver and muscle. Life Sciences 31(15):15871596, 1982. Thus, glucocorticoids bind to mineralocorticoid (type 1) receptors and glucocorticoid (type 2) receptors in the hypothalamus, hippocampus, and pituitary. Several mechanisms may contribute to alcohols effects on the various hormones involved in the male HPG axis: The HPT axis is responsible for maintaining normal circulating levels of the thyroid hormones thyroxin (T4) and its active form, triiodothyronine (T3). PMID: 3122774, Van Cauter, E.; Latta, F.; Nedeltcheva, A.; et al. Moreover, in both groups the total integrated response value for insulin was significantly higher after oral glucose administration than after intravenous administration, suggesting a potentiating incretin2 effect on insulin secretion. Alcohol is made up of toxins and, therefore, negatively affects many different and vital parts of your body. 2000). PMID: 2239905, Hotamisligil, G.S. PMID: 10857962, Welsch, T.; Kleeff, J.; Seitz, H. K.; et al. Ethanol inhibits luteinizing hormone-releasing hormone release from the median eminence of prepubertal female rats in vitro: Investigation of its actions on norepinephrine and prostaglandin-E2. Finally, people with a family history of alcohol use disorder (AUD) exhibited hyperresponsiveness of the stress response mediated by the HPA axis (Uhart et al. She helps individuals recover from drug, alcohol and gambling dependencies through group and individual therapy and regularly speaks at treatment centers. Effects of drug and alcohol abuse upon pituitary-testicular function in adolescent males. Our website is not intended to be a substitute for professional medical advice, diagnosis, or treatment. PMID: 395267, Sarkar, D.K. Autocrine: A mode of hormone action in which a hormone binds to receptors on, and affects the functions of, the cell type that produced it. Inhibition of nitric oxide synthase prevents the alcohol-induced decrease in testosterone (Adams et al. Hypothalamic releasing and inhibiting hormones are carried directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. ; Simonyl, A.; and Rudeen, P.K. Blood 96(5):17231732, 2000. Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women. Alcohol abuse can result in clinical abnormalities of one of the bodys most important systems, the endocrine system. PMID: 26519603, Majumdar, S.K. Taxing the liver with alcohol can make . PMID: 18709650, Sierksma, A.; Patel, H.; Ouchi, N.; et al. Their results were published in the September issue of Psychopharmacology. PMID: 7738205, Kang, L.; Sebastian, B.M. PMID: 18191055, Beulens, J.W. PMID: 3172983, Soszynski, P.A., and Frohman, L.A. Inhibitory effects of ethanol on the growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-I axis in the rat. Ethanol induces hyperprolactinemia by increasing prolactin release and lactotrope growth in female rats. These changes are associated with decreased D2R mRNA and protein. PMID: 2263621, Plant, T.M. Leptin acts centrally to induce the prepubertal secretion of luteinizing hormone in the female rat. Moreover, recent studies have demonstrated that peripheral administration of oxytocin can reduce ethanol consumption in rats (MacFadyen et al. Endocrine 14(2):213219, 2001b. CRF release by cells from the PVN of the hypothalamus activates this BEP synthesis and release, which then inhibits further CRF release, creating a negative feedback cycle (Plotsky et al. Alcohol is transported throughout a body in the bloodstream and spreads to every organ through the body's water. Ataxia refers to a loss of coordination, making it impossible to control various body movements. PMID: 11739329, Chaturvedi, K., and Sarkar, D.K. Eating Disorders and Hypothalamic Amenorrhea. Growth hormonereleasing hormone (GHRH) secreted from cells in the arcuate and ventromedial nuclei of the hypothalamus into the hypophyseal portal system acts on somatotropic cells in the anterior pituitary, stimulating them to synthesize and release GH into the general circulation. Journal of Pharmacology and Experimental Therapeutics 245(3):895904, 1988. 1998). Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Severe damage to these neurons could cause a user to experience symptoms of depression, paranoia and hallucinations. Alcohol consumption and risk of cancer: A systematic literature review. Total Integrated Response: A measure of the area under the curve of the insulin or glucose response to an oral glucose challenge used to determine insulin resistance. Alcohol-related pancreatic damage: Mechanisms and treatment. 2007). 2000) since IGF-1 can stimulate testosterone synthesis and spermatogenesis (Roser 2008). PMID: 22302180, Nagy, L.E. Chronic alcohol ingestion decreases pituitary-thyroid axis measures in Fischer-344 rats. These islet cells can be further subdivided into - and -cells. Glucokinase is involved in glucose metabolism that leads to increased production of adenosine-triphosphate, a necessary step in insulin secretion by -cells. Endocrine Reviews 17(1):64102, 1996. 2 2008; Strbak et al. A second component of the stress response is the fight-or-flight response of the sympathetic nervous system, which acts as the first line of defense against stressors. As outlined above, severe risks are associated with abusing alcohol for long periods of time. Drinking alcohol can impair the functions of the glands that release hormones and the functions of the tissues targeted by the hormones, which can result in medical problems. Accountability is a vital and required part of sustaining recovery. PMID: 16489593, Verbalis, J.G. Annals of the New York Academy of Sciences 689:146160,1993. doi:10.3390/biom5042223, Gaddini GW, Turner RT, Grant KA, Iwaniec UT. 6. There are promising preclinical animal studies of DBS for alcohol consumption as well as some initial human clinical studies that have shown some promise . 1988) found that 50 percent of social (i.e., about 3.84 drinks per day) and 60 percent of heavy (i.e., about 7.81 drinks per day) healthy, nondependent drinkers exhibited significant disturbances of their reproductive hormones and menstrual cycle compared with occasional drinkers (i.e., about 1.22 drinks per day). Alcohol is classified as a central nervous system depressant. ; Ajmo, J.M. ; Verma, P.; and Weinberg, J. PMID: 1656797, Aoun, E.G. Endocrinology 141(4):13251331, 2000. Other studies have shown that long-term moderate alcohol consumption can decrease the number and quality of a womans oocytes (i.e., ovarian reserve), which was associated with increased FSH levels (Li et al. ; Boldt, B.M. Nitric oxide, which is synthesized in the testes by nitric oxide synthase, is another proposed player in the alcohol-induced reduction of testosterone production. 1995) and the development of hypogonadism (Castilla-Cortazar et al. Alcoholism: Clinical and Experimental Research 27(6):975980, 2003. Mice lacking a functional CRF1 receptor progressively increased their ethanol intake when subjected to repeated stress; this effect seemed to persist throughout their life (Sillaber et al. ; and Swaab, D.F. Long-term changes in the hypothalamo-pituitary-adrenal axis. ; and Herman, J.P. Neural regulation of the stress response: The many faces of feedback. Scientists believe that alcohol-seeking behavior is regulated in part by the hypothalamic pituitary adrenal axis. Life Sciences 50(6):PL35PL40, 1992. This can cause injuries, poor decision-making, and other detrimental events that can affect the rest of your life. This binding decreases CRF, AVP, and ACTH production (figure 1). The alcohol metabolite acetaldehyde can disrupt testosterone production by inhibiting protein kinase C, a key enzyme in testosterone synthesis (Chiao and Van Thiel 1983). the testes, and the hypothalamus.2 Alcohol affects each of these parts of the male reproductive system, preventing . PMID: 9727642, Maeda, N.; Shimomura, I.; Kishida, H.; et al. 2016) and that intranasal oxytocin administration blocks alcohol withdrawal in humans (Pedersen et al. If the user continues drinking, the hypothalamus and amygdala become affected. Alcohol 18(23):109122, 1999. Endocrine Reviews 30(2):152177, 2009. Both acute and chronic exposure to alcohol may have differential direct and indirect effects on endocrine functions. At this stage, the individual experiences permanent memory loss and confabulation (creation of new but untrue memories), learning problems, hallucinations, unsteadiness on his or her feet, and dementia. 1991). Upon thermogenic activation, the type II thyroxine 5-deiodinase enzyme, which is expressed specifically in BAT, converts T4 into T3 (de Jesus et al. Alcoholism: Clinical and Experimental Research 24(12):18361849, 2000. Nadia Rachdaoui, Ph.D., is an assistant research professor, and Dipak K. Sarkar, Ph.D., D.Phil., is Board of Governors Distinguished Professor, in the Rutgers Endocrine Research Program, Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey. Hormone and Metabolic Research 28(12):619632, 1996. Neuroadaptive functions of the neuropeptide arginine vasopressin. 1986). Impair the hormonal response to hypoglycemia with heavy consumption. At the anterior pituitary, CRF binds to CRF1 receptors and stimulates specific cells (i.e., corticotropic cells) to synthesize and secrete a peptide called proopiomelanocortin (POMC). Alcohol also may damage the bacterial flora in the gut as well as the intestinal walls, leading to the release and transfer into the blood of bacterial lipopolysaccharides, which play a key role in alcohol-mediated inflammation (Purohit et al. Diabetes Care 23(1):1822, 2000. ; Leserman, J.; et al. Alcohol can also affect sperm structure, menstruation, ovulation and increase the risk of miscarriage and fetal development. The cause of the alcoholic gait is brain damage called alcoholic cerebellar ataxia. 2004). ; and Teoh, S.K. 1988). For those with severe addiction, rehabilitation or detoxification may be the best first step in a treatment plan. A bidirectional interaction between the HPA axis and the immune system also may contribute to alcohol-induced inflammatory reactions. Nature 372(6505):425432, 1994. Numerous studies have documented alcohols diverse deleterious effects on the HPG axis and its hormones (figure 2). 2002), suggesting that alcohols effects during puberty partly may result from an increased opioid restraint on the normal progression of pubertal processes. Hepatology 31(6):1379, 2000. PMID: 8742123, Navarro, V.M. PMID: 18330713, Dong, H.; Kumar, M.; Zhang, Y.; et al. Asian Pacific Journal of Cancer Prevention 14(9):49654972, 2013. It can also:. ; Song, E.H.; Lee, H.J. The medulla is the section of the brain that regulates the body . ; et al. PMID: 10688896, MacFadyen, K.; Loveless, R.; DeLucca, B.; et al. . Readall about H.M.s incredible story. We have been taught that alcohol has toxins, but at what point does that negatively change our most important organ: the brain? Alcohol affects your brain in ways that lead to more eating, but there are actions you can take to avoid putting on unwanted weight from eating under the influence. After a brief overview of the hormones of the hypothalamus and pituitary gland, this article discusses the adverse effects of both acute and chronic alcohol exposure on the different components of these hormone systems based on recent findings from human and animal studies. These studies clearly indicate that chronic exposure to alcohol attenuates basal ACTH and corticosterone levels and increases anxiogenic-like behaviors. If a user continues to drink at this point, it may affect the brain stem, which induces sleep and can cause irregular breathing and even seizures. 2013; Haas et al. Sobriety is challenging, but your health is worth it. Through this transmission of neurons, our brain becomes active and can process the skills and responses required to function. Genetics certainly influence our likelihood of developing AUD, but the story isn't so simple. Regulation of testicular function in the stallion: An intricate network of endocrine, paracrine and autocrine systems. However, prolactin also has been implicated in a plethora of other biological functions or responses, such as mammary-gland development; reproduction; immune functions; and behavioral functions, including learning, memory, and adaptation. Alcoholism abolishes the growth hormone response to sumatriptan administration in man. ; Nock, B., Truong, R.; and Cicero, T. J. Nitric oxide control of steroidogenesis: Endocrine effects of NG-nitro-L-arginine and comparisons to alcohol. PMID: 18504085, Rasmussen, D.D. These coordinated bidirectional interactions rely on the production and release of chemical messengers, such as neurotransmitters, hormones, and cytokines, that mediate the communications between the different systems. 2003). These gonadotropins regulate the development of follicles (i.e., folliculogenesis) in females and of sperm (i.e., spermatogenesis) in males. Hormones play an important role in maintaining calcium levels in the body, which is necessary not only for strong bones and teeth but also for communication between and within cells of the body. However, AVP and oxytocin also can be produced in another group of neurons in the PVN and supraoptic nuclei (i.e., in the parvocellular neurons) and released into the hypothalamichypophyseal portal vessels to reach the anterior pituitary. The analyses demonstrated that during early abstinence, the GH response to these different secretagogues, which include such neurotransmitters as dopamine, norepinephrine, acetylcholine, -aminobutyric acid (GABA), and serotonin, also is altered. Common manifestations of hyperprolactinemia in women include lack of menstrual cycles (i.e., amenorrhea) and excessive or spontaneous secretion of milk (i.e., galactorrhea). Sillaber, I.; Rammes, G.; Zimmermann, S.; et al. Excessive use of alcohol causes a variety of chemical and molecular alterations within the brain that forms the basis of several behavioral and physical manifestations. However, more studies are needed to help with our understanding of the adipose tissue pathology associated with alcohol abuse. ; Walker, C.H. ; et al. 2001; Obradovic and Meadows 2002), decreased (Calissendorff et al. In a study comparing behaviorally dependent and ethanol-exposed but nondependent rats, Baumgartner and colleagues (1997) found that the activity of 5II deiodinase was elevated in the frontal cortex in both groups of rats. This delay could be prevented by naltrexone, an antagonist of the opioid receptors (Emanuele et al. Chronic alcohol consumption also is a known independent risk factor for the development of type 2 diabetes (Hodge et al. Currents in Alcoholism 8:359378,1981. In: Kusnecov, A., and Anisman, H., Eds. The frontal lobe is responsible for decision making, and when impaired by alcohol, it can become difficult for people to think clearly and make good decisions. The hippocampus is the part of the brain where memories are made. 1995). Alcoholism: Clinical and Experimental Research 26(2):255262, 2002. Effects on pubertal hormones by ethanol abuse in adolescents. Consuming one makes your hypothalamus signal that you're craving the other. Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats. However, a discussion of this evidence and the proposed mechanisms is beyond the scope of this article. This is why intoxicated people may be more likely to fall or have slurred speech. PMID: 25456265, Wei, M.; Gibbons, L.W. ; Herzenstiel, M.N. When alcohol impairs the hormone system's ability to work properly, it can disrupt these major bodily functions: 1 Growth and development Maintenance of blood pressure and bone mass Production, utilization, and storage of energy Reproduction Chronic alcohol consumption also is a risk factor for the development of pancreatic cancer, with moderate to heavy consumption increasing the risk both alone and in combination with other risk factors, such as tobacco and obesity (de Menezes et al. 2013). Drinking excessively over an extended period of time can lead to problems with cognition and memory. 1992). Figure 3.2Originally named for its resemblance to a seahorse (genusHippocampus) the hippocampus is a small curved structure located within the temporal lobes of the brain (one in each hemisphere). ; Sliwowska, J.H. Another hormone called somatostatin, which is secreted from the PVN of the hypothalamus, also acts on the pituitary and inhibits GH secretion. . At this point of consumption, the user can be described as someone who is acting on animal instincts since all parts of the brain that regulate human reasoning have gone offline. 2013). Alcohol can interfere with the function of each of these components, thereby causing impotence, infertility, and reduced male secondary sexual characteristics. During final processing of the insulin molecule, the C-peptide is removed to yield the functional insulin molecule with its two chains.2 Incretin is a hormone secreted by the wall of the intestine that acts on the pancreas to regulate insulin production after glucose administration. Alcohol consumption, in most cases, does not cause permanent brain damage in reasoning, memory, or other forms of cognition. Four-week ethanol intake decreases food intake and body weight but does not affect plasma leptin, corticosterone, and insulin levels in pubertal rats. 1998) by alcohol exposure. 1988). Thus, exposure to 100 mM ethanol directly inhibited LHRH release from incubated medial basal hypothalamic sections, and this effect was reversed by naltrexone (Lomniczi et al. The investigators suggested that alcohol exposure led to a downregulation and inactivation of the enzyme glucokinase, which acts as a -cell sensor for blood glucose levels. PMID: 16325293, Uhart, M.; Oswald, M.; McCaul, M.E. PMID: 8749812, Terasawa, E., and Fernandez, D. L. Neurobiological mechanisms of the onset of puberty in primates. Alcoholism: Clinical and Experimental Research 32(5):806813, 2008. ; and Zimmet, P.Z. The AUD group also had significantly lower semen volume, sperm count, motility, and number of morphologically normal sperm (Muthusami and Chinnaswamy 2005). To understand the effects alcohol causes, its important to understand the different parts of the brain and alcohols impact on them. Alcohol-related bone health problems pose a serious health threat for alcoholics due to the greater risks of falls and therefore fractured or broken bones. In addition, experiments in another cultured -cell line indicated that heavy alcohol consumption may induce -cell dysfunction in type 2 diabetes by increasing the production of reactive oxygen species and inducing apoptosis in the cells (Dembele et al. For example, men with AUD exhibited impairments both in the serotonin-mediated stimulation of GH secretion (Coiro and Vescovi 1995) and in melatonins effect on basal and hypoglycemia-induced GH secretion (Coiro and Vescovi 1998) during early abstinence. Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats. Over time with repeated use of alcohol especially by people who binge drink alcohol can cause actual damage to the hippocampus leading to more sustained cognitive and memory problems. PMID: 12450316, Hiney, J.K., and Dees, W.L. ; Schwandt, M.L. Alcoholism: Clinical and Experimental Research 26(9):14201429, 2002. ; Bree, M.P. LHRH then triggers the pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting in subsequent ovarian maturation (Plant 2015). This part of the stress response also is regulated by BEP produced from POMC in the hypothalamus, which not only modulates CRH release but also can help decrease the stress response and return the body to a state of homeostasis.2 BEP binds with high specificity to different receptors (i.e., - and -opioid receptors), thereby inhibiting the sympathetic nervous system response to stress. PMID: 22198308, Meinhold, C.L. Verywell Mind articles are reviewed by board-certified physicians and mental healthcare professionals. Some studies found normal concentrations of total plasma T4 (tT4) during early withdrawal (Majumdar et al. In response to signals from the hypothalamus, the anterior pituitary produces and secretes trophic hormones, which are hormones that have a growth effect on the organs or tissues they are targeting. Alcohol Clin Exp Res. At the same time, the AVP binds to V1b receptors, potentiating the effects of CRF on ACTH production in the anterior pituitary. This thyroid dysfunction can recover after longer periods of abstinence, with thyroid hormones and the TSH response to TRH returning to normal levels (Pienaar et al. 2, Part of the These hormones facilitate an immediate reaction by triggering physiological changes, such as increased heart rate and respiration, and provide the body with a burst of energy through the release of sugar (i.e., glucose) and fat into the bloodstream as energy sources that help the body to respond to the stressors and fight off the threat. PMID: 25913220, Sarkar, D.K., and Fink, G. Mechanism of the first spontaneous gonadotrophin surge and that induced by pregnant mare serum and effects of neonatal androgen in rats. Furthermore, in a study of 4,649 healthy individuals who were exposed to increasing levels of alcohol, Knudsen and colleagues (2001) found an association between a reduced thyroid gland volume and a lower risk of developing goiter or solitary nodules. Jenkins and Connolly (1968) showed that plasma cortisol levels significantly increased in healthy subjects at alcohol doses exceeding 100 mg/dL. The activity of the HPA axis is regulated through several feedback mechanisms. The more alcohol you consume, the more at risk you are for chronic anxiety, depression, and AUD, as this cycle is hard to break and leaves you craving the boost of neurons, like dopamine, once again. Alcohol causes inflammation in a part of your brain called the hypothalamus, which disrupts your brain's ability to receive signals related to insulin needs in the body. It happens to people who are long-term alcohol-dependent because alcohol blocks the absorption of thiamine.. Therefore, some problems like bloating, gassiness, or diarrhea can occur. Read our. Hegedus, L.; Rasmussen, N.; Ravn, V.; et al. Psychoneuroendocrinology 22(1):1324, 1997. Little research has assessed the effects of alcohol use on the hypothalamicpituitarygonadal (HPG) axis during puberty in humans. The effect of binge ethanol exposure on growth hormone and prolactin gene expression and secretion. Conversely, several hypothalamic factors stimulate prolactin release from the anterior pituitary, including thyrotropin-releasing hormone, vasoactive intestinal peptide, oxytocin, -endorphin, neurotensin, substance P, serotonin, and prostaglandins. Elevated prolactin levels also were reported in women with AUD and admitted for alcoholism treatment who reported drinking an average of 84 g of alcohol (i.e., approximately 7 standard drinks) per day for at least 7 years (Seki et al. Diabetes Care 27(5):1240, 2004. These types of communities can make you feel less alone and offer you a place to speak without fear of ridicule or judgment. Effect of chronic ethanol exposure on female rat reproductive cyclicity and hormone secretion. People with alcohol addiction risk getting head, neck, liver, esophageal, breast, or colorectal cancer.. Lastly, your bodys overall functions and health are negatively affected by consuming too much alcohol. ; Krampe, H.; et al. Several studies clearly have demonstrated that ethanol exposure during the developmental period induced neurotoxicity and permanent impairments in the HPA axis that were associated with immune dysfunction (Hellemans et al. ; et al. 1987). 1995). Alcohol, slow wave sleep, and the somatotropic axis. The ability of alcohol to cause short term memory problems and blackouts is due to its effects on an area of the brain called the hippocampus. Brown adipocytes are smaller than white adipocytes, have numerous mitochondria, and specialize in heat production through oxidation of fatty acids (i.e., thermogenesis). IUBMB Life 60(12):790797, 2008. Inverse relationship between CSF TRH concentrations and the TSH response to TRH in abstinent alcohol-dependent patients. Frontiers of Hormone Research 38:3241, 2010. These increased estradiol levels could in part explain alcohols negative effects on menstrual cycle regularity. Federal government websites often end in .gov or .mil. Does LHRH meet the criteria for a hypothalamic releasing factor? However, recent direct and indirect evidence also suggests a potential endocrine role for BAT (Villarroya et al. Depending on its location, WAT synthesizes and secretes different sets of adipokines (Coelho et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice.