Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss.

OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids.

Therapeutic Options in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.

Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery.

OBJECTIVE: To examine the impact of important weight loss on insulin inhibition of its own secretion during experimentally induced hyperinsulinemia under euglycemic conditions. DESIGN: Longitudinal, clinical intervention study--bariatric surgery (vertical banded gastroplasty--gastric bypass--Capella technique), re-evaluation after 4 and 14 months. SUBJECTS: Nine obese patients class III (BMI=54.6+/-2.6 kg/m2) and nine lean subjects (BMI=22.7+/-0.7 kg/m2). MEASUREMENTS: Euglycemic hyperinsulinemic clamp (insulin infusion: 40 mU/min m2), C-peptide plasma levels, electrical bioimpedance methodology, and oral glucose tolerance test (OGTT). RESULTS: BMI was reduced in the follow-up: 44.5+/-2.2 and 33.9+/-1.5 kg/m2 at 4 and 14 months. Insulin-induced glucose uptake was markedly reduced in obese patients (19.5+/-1.9 micromol/min kg FFM) and improved with weight loss, but in the third study, it was still lower than that observed in controls (35.9+/-4.0 vs 52.9+/-2.2 micromol/min kg FFM). Insulin-induced inhibition of its own secretion was blunted in obese patients (19.9+/-5.7%, relative to fasting values), and completely reversed to values similar to that of lean ones in the second and third studies (-60.8+/-4.2 and -54.0+/-6.1%, respectively).CONCLUSION: weight loss in severe obesity improved insulin-induced glucose uptake, and completely normalized the insulin inhibition on its own secretion.

Factors of importance for weight loss in elderly patients with Parkinson's disease.

OBJECTIVE: weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. PARTICIPANTS AND METHODS: Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. RESULTS: Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. CONCLUSION: weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Snoring and Sleep Apnea in Obese Adolescents: Effect of Long-term weight loss-Rehabilitation.

Objective: To test the effect of a long-term weight loss rehabilitation program in extremely obese adolescents on breathing parameters during sleep. Methods: Thirty-eight extremely obese [mean body mass index (BMI) 45.3 +/- 7.9kg/m(2)] adolescents participated during a three- to nine-month period in an inpatient weight loss rehabilitation in a specialized long-term rehabilitation center. Breathing parameters were registered via a seven-channel portable screening device. Body weight and arterial blood pressure were measured before and after the long-term treatment. Results: Mean BMI decreased from 45.3 to 35.8 (p < 0.001), mean diastolic blood pressure decreased from 89 mmHg to 81 mmHg (p = 0,002). Nine patients had a RDI of >/=5 and 30 patients a RDI of <5; the mean RDI decreased from 4.08 to 3.27 (n.s.). Within the group, the RDI was >/=5 and the mean RDI decreased from 10.3/h to 5.2/h (p = 0.02). The mean SaO2 increased from 93.65 to 95.35% (p = 0.003), lowest SaO2 increased from 72.14 to 73.19% (n.s.) and snoring frequency decreased from 37.56% of total sleep time (TST) to 32.86% of TST (n.s.). Conclusion: A long-term inpatient weight loss program has a positive effect on breathing parameters during sleep in extremely obese adolescents. However, the effect on apneic events and snoring is relatively minor compared to the effect on arterial oxygen saturation. The role of obesity in the origin of respiratory events and snoring in adolescents might be overestimated.

Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study.

OBJECTIVE: To examine the association of voluntary vs involuntary weight loss with incidence of cancer in older women. DESIGN: Prospective cohort study from 1993 to 2000, with cancer incidence identified through record linkage to a cancer registry. SUBJECTS: A total of 21,707 postmenopausal women initially free of cancer. MEASUREMENTS: Women completed a questionnaire about intentional and unintentional weight loss episodes of > or =20 pounds during adulthood. RESULTS: Compared with women who never had any > or =20 pounds weight loss episode, women who ever experienced intentional weight loss > or =20 pounds but no unintentional weight loss had incidence rates lower by 11% for any cancer (RR=0.89, 95% CI 0.79-1.00), by 19% for breast cancer (RR=0.81, 95% CI 0.66-1.00), by 9% for colon cancer (RR=0.91, 95% CI 0.66-1.24), by 4% for endometrial cancer (RR=0.96, 95% CI 0.61-1.52), and by 14% for all obesity-related cancer (RR=0.86, 95% CI 0.74-1.01) after adjusting for age, body mass index, waist-to-hip ratio, physical activity, education, marital status, smoking status, pack-years of cigarettes, current estrogen use, alcohol use, parity, and multivitamin use. Furthermore, although overweight women were at increased risk of several cancers, women who experienced intentional weight loss episodes of 20 or more pounds and were not currently overweight were observed to have an incidence of cancer similar to nonoverweight women who never lost weight. Unintentional weight loss episodes were not associated with decreased cancer risk. CONCLUSIONS: These findings suggest that intentional weight loss might reduce risk of obesity-related cancers.

Weight reduction, fertility and contraception.

PIP: The significance of weight and body composition with regard to the fertile menstrual cycle has excited much interest. There is global imbalance of resources and problems of widespread chronic malnutrition in many 3rd world countries. This emphasizes the great importance of the possible effects of diet, body weight, and body composition on fecundity (ability to reproduce), fertility (reproductive performance), and pregnancy outcome. Frisch and Revelle suggested that a critical body weight is required for a girl to progress through puberty, menstruate, and finally develop ovulatory cycles. They postulated a direct relationship between weight and menarche and suggested that before menarche will occur at least 17% of the body weight needs to be made up of fat. The Frisch hypothesis is not universally accepted, and it seems highly unlikely that a single age unrelated body weight is always the trigger for menarche. Many of the data used in Frische's original studies were derived rather than directly observed. It seems likely that both body weight and composition are important and that the peripheral conversion of androgens to estrogens in fat plays a role in pubertal development, but the actual signal whcih triggers the hypothalamic events leading eventually through puberty to menstruation and ovulation remains unkown. Acute malnutrition, as seen during famine, is assoicated with a dramatic decrease in fertility. It is usually secondary to amenorrhea and annovulation. In developing countries weight related amenorrhea and delayed menarche are largely the result of nutritonal deprivation and the demands of lactation on women of boderline body weight, but a different pattern is seen in Western countries. The outstanding example of weight reduction resulting in infertility is seen in patients with anorexia nervosa. These women have extreme self imposed weight loss, a distorted perception of their body image, and disturbance in their attitude towards their feelings of hunger and satiety. Self imposed weight loss is the most common single cause of secondary amenorrhea seen in the Western world. While diagnosis of the gross anoretic is perhaps rarely missed, the more subtle degrees of weight loss and their effect on the menstrual cycle are often overlooked. Simple weight loss of more than 30% of body fat will cause menstrual dysfunction and ultimately amenorrhea. There is no clearly defined threshold between infertility and normal reproductive health, and there will always be women who become pregnant despite suboptimal weight. Patients with simple weight loss may be sufficiently motivated to restore their weight to normal levels, with resultant spontaneous resumption of ovulation.

Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.