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Metformin, the world's most prescribed anti-diabetic drug, is also effective in preventing type 2 diabetes in people at high risk.sup.1,2. More than 60% of this effect is attributable to the ability of metformin to lower body weight in a sustained manner.sup.3. The molecular mechanisms by which metformin lowers body weight are unknown. Here we show--in two independent randomized controlled clinical trials--that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor. In wild-type mice, oral metformin increased circulating GDF15, with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to a high-fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GDNF family receptor [alpha]-like (GFRAL). In obese mice on a high-fat diet, the effects of metformin to reduce body weight were reversed by a GFRAL-antagonist antibody. Metformin had effects on both energy intake and energy expenditure that were dependent on GDF15, but retained its ability to lower circulating glucose levels in the absence of GDF15 activity. In summary, metformin elevates circulating levels of GDF15, which is necessary to obtain its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent. In mouse studies, metformin treatment results in increased secretion of growth/differentiation factor 15 (GDF15), which prevents weight gain in response to high-fat diet, and GDF15-independent lowering of circulating blood glucose., Author(s): Anthony P. Coll [sup.1] , Michael Chen [sup.2] , Pranali Taskar [sup.2] , Debra Rimmington [sup.1] , Satish Patel [sup.1] , John A. Tadross [sup.1] , Irene Cimino [sup.1] [...]

The case of an 81-year old man who is suffering from weight loss and odynophagia is discussed to better understand the causes, symptoms, diagnosis and treatment pf advanced HIV infection. The need and importance of early detection of HIV infection through HIV testing is highlighted.

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n 14) or placebo (n - 15) with a macronutrient energy distribution of ~10% carbohydrate, ~65% fat, and ~25% protein. Because the groups did not differ in any of the variables measured, ali data were pooled and comparisons were made between baseline and 12 wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P < 0.001), and abdominal fat was reduced by 20% (P < 0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (13.8%), C-III (-21.2%) and E (-12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P < 0.05). Changes in plasma TG were positively correlated with reductions in large (r = 0.615, P < 0.01) and medium VLDL particles (r0.432, P < 0.05) and negatively correlated with LDL diameter (r = -0.489, P < 0.01). Changes in trunk fat were positively correlated with medium VLDL (r = 0.474, P < 0.0) and small LDL (r = 0.405, P < 0.05) and negatively correlated with large HDL (r = -0.556, P < 0.01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease. KEY WORDS: * carbohydrate restriction * weight loss * lipoprotein metabolism * LDL size * HDL subclasses

The six-month risk and determinants of greater than or equal to 5% weight loss during the period when the use of combination antiretroviral therapy and highly active antiretroviral therapy (HAART) was commonplace among participants of a cohort study in Boston between 1995 and 2003, was examined. Findings reveal that the risk of greater than or equal to 5% unintentional weight loss over 6-month intervals is on the rise in cohort of HIV-infected participants, despite better control of HIV infection.

An attempt is made to test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. The result indicates that changes in dietary composition within prevailing norms can affect physical adaptations that defend body weight.

Byline: Pei-Ning Wang (1), Chueh-Lien Yang (3), Ker-Neng Lin (1), Wei-Ta Chen (1), Leh-Chii Chwang (3), Hsiu-Chih Liu (1,2) Keywords: nutrition; nutritional status; physical activities; weight loss; Alzheimer's disease Abstract: Abstract. The etiology of weight loss in Alzheimer's disease (AD) patients is still uncertain. This study was designed to investigate the possible factors that might contribute to weight change of AD patients. From July 1999 to June 2001, we recruited 51 AD patients and 27 non-demented controls. Demographic data, neuropsychological tests, Geriatric Depression Scale-Short Form, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. More than half of our AD patients developed body weight loss, and overall, the AD patients were significantly thinner than the non-demented subjects. Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients. The AD patients had fewer daily physical activities. More AD patients had the problem of poor appetite. However, daily calorie intake was not significantly different between the two groups. The AD patients, especially those who presented with body weight loss, even consumed more calories per body weight kilogram (kg) per day. In the food composition analysis, AD patients took more carbohydrate than controls. Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss. We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients, and that these changes contribute to the weight loss. Author Affiliation: (1) Neurological Institute, Taipei Veterans General Hospital and Dept. of Neurology, National Yang-Ming University, School of Medicine, Taipei, Taiwan (2) The Neurological Institute, Taipei Veterans General Hospital, No. 201 Shih-Pai Road, Sec. 2, Taipei 112, Taiwan (3) Dept. of Food and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan Article History: Registration Date: 01/01/2004 Received Date: 11/06/2003 Accepted Date: 22/10/2003

Little is known about the relative effects of fermentable fiber (FF) vs. nonfermentable fiber (NFF) on energy regulation in humans. We compared 27 [+ or -] 0.6 g/d supplements of FF (pectin,/[beta]-glucan) and NFF (methylcellulose) for their ability to decrease ad libitum energy intake (El) and hunger, increase satiety and cause spontaneous body weight and fat losses. Men and women (n = 11) aged 23-46 y, BMI 20.0-34.4 kg/[m.sup.2], consumed first NFF and then FF for 3 wk each, with a 4-wk washout period between phases. Daily satiety assessed with analog scales was higher with NFF than FF (60.7 [+ or -] 1.0 vs. 57.7 [+ or -] 0.8 mm, P = 0.01). However, there were no differences in reported El (NFF < FF by 7%, P = 0.31, NFF < baseline by 9.5%, P = 0.11), body weight (NFF 0.13 kg, P = 0.73; FF 0.13 kg, P = 0.60) or fat percentage (NFF -0.3%, P = 0.56; FF -0.1%, P = 0.66) within either phase. In contrast to findings in animals, NFF was more, rather than less satiating than FF, and use of neither NFF nor FF preparations was associated with body weight or fat loss. These pilot results suggest no role for short-term use of FF and NFF supplements in promoting weight loss in humans consuming a diet ad libitum. J. Nutr. 133: 3141-3144, 2003. KEY WORDS: * fiber * fermentable * nonfermentable * satiety * weight loss

Objective. Some mothers have difficulty initiating lactation even when highly motivated to breastfeed. The purpose of this study was to determine the incidence of and risk factors for suboptimal infant breastfeeding behavior (SIBB), delayed onset of lactation, and excess neonatal weight loss among mother-infant pairs in a population with high educational levels and motivation to breastfeed. Methods. All mothers residing in Davis, California, who gave birth to a healthy, single, term infant at 1 of 5 area hospitals during the 10-month recruitment period in 1999 were invited to participate if they were willing to attempt to breastfeed exclusively for at least 1 month. Lactation guidance was provided and data were collected in the hospital (day 0) and on days 3, 5, 7, and 14. Infant breastfeeding behavior was evaluated by trained lactation consultants using the Infant Breastfeeding Assessment Tool. Onset of lactation was defined based on maternal report of changes in breast fullness. Infant weight loss was considered excessive if it was [greater than or equal to] 10% of birth weight by day 3. Results. Of the 328 eligible mothers, 280 (85%) participated in the study. The prevalence of SIBB was 49% on day 0, 22% on day 3, and 14% on day 7. SIBB was significantly associated with primiparity (days 0 and 3), cesarean section (in multiparas, day 0), flat or inverted nipples, infant status at birth (days 0 and 3), use of nonbreast milk fluids in the first 48 hours (days 3 and 7), pacifier use (day 3), stage II labor >1 hour (day 7), maternal body mass index >27 kg/[m.sup.2] (day 7) and birth weight 72 hours) occurred in 22% of women and was associated with primiparity, cesarean section, stage II labor >1 hour, maternal body mass index >27 kg/[m.sup.2], flat or inverted nipples, and birth weight >3600 g (in primiparas). Excess weight loss occurred in 12% of infants and was associated with primiparity, long duration of labor, use of labor medications (in multiparas), and infant status at birth. The risk of excess infant weight loss was 7.1 times greater if the mother had delayed onset of lactation, and 2.6 times greater if the infant had SIBB on day 0. Conclusions. Early lactation success is strongly influenced by parity, but may also be affected by potentially modifiable factors such as delivery mode, duration of labor, labor medications, use of nonbreast milk fluids and/or pacifiers, and maternal overweight. All breastfeeding mother-infant pairs should be evaluated at 72 to 96 hours&apos; postpartum. Pediatrics 2003;112:607-619; breastfeeding, infant suck, lactogenesis, cesarean delivery., The first week postpartum is a critical period for the establishment of breastfeeding. Normally, the amount of milk produced is minimal for the first 1 to 2 days' postpartum, but [...]

A 79-year-old man who had lost 30% of his body weight over a six-month period was found to have severe atherosclerosis affecting the blood vessels in his stomach. This is such an unusual condition that his doctors spent much of their time trying to find cancer, which is a much more common cause of severe weigh loss. He received a bypass much like the kind used to treat coronary artery disease and he regained the weight he had lost.

The objective of this study was to investigate whether nursing a large number of piglets has negative effects on lactation and postweaning performance of primiparous sows and whether a greater lactation feed intake can prevent possible negative effects. Data were recorded on 268 ad libitum-fed sows of three genotypes (G1, G2, and G3) in an experiment where litter size was standardized to 8, 11, or 14 piglets during a 4-wk lactation. Compared to G1 and G2, G3 sows were heavier (P < 0.05) and leaner (P < 0.05) at weaning of their litters, lost similar amounts of BW and backfat, and their piglets grew faster (P < 0.05). Compared to G1, feed intake during lactation was higher for G3 sows (P < 0.05), and their risk of a prolonged weaning-to-estrus interval was lower (P < 0.01). Daily feed intake by sows was not affected by litter size in G1 and G3, but it was quadratically affected in G2 (P < 0.05), with a maximum at 10.8 piglets. Backfat loss of the sows increased linearly with litter size (P < 0.05) in G1 and G3. In G2, backfat loss increased only at litter sizes > 9.8 piglets (P < 0.01). Body weight loss of the sow and litter weight gain increased linearly with litter size (P < 0.001). Per extra piglet nursed, sows had a 23% (P < 0.01) higher probability of a prolonged weaning-to-estrus interval. A higher daily feed intake during lactation reduced tissue loss of the sow, increased litter weight gain (P < 0.01), and reduced the probability of a prolonged weaning-to-estrus interval (by 42% per extra kilogram; P < 0.01). Sows with a lower daily body weight loss during first lactation had a larger second litter (1.28 piglets/kg; P < 0.01), and their probability of a prolonged weaning-to-estrus interval was reduced by 61% per kilogram (P < 0.001). With increasing litter size, it is therefore recommended to reduce body weight loss during lactation by stimulating daily feed intake and by genetic selection. Key Words: Backfat, Feed Intake, Litter Size, Reproductive Performance, Sows, Weight Losses

Research has been conducted on the weight loss and wasting, the features of HIV progression. The hypothesis that wasting is still associated with decreased survival in the patients who received highly active antiretroviral therapy has been tested, and the identification of the more basic body composition and wasting measuring technique associated with mortality in HIV-infected persons has been carried out and discussed.

Byline: D. M. Premer (1,2), R. Goertz (1,2), M. K. Georgieff (1,2), M. C. Mammel (1,2), S. J. Schwarzenberg (1,2,3) Keywords: Sepsis; protein; muscle; neonate Abstract: Our hypothesis is that nitrogen loss in septic neonates is caused by increased muscle proteolysis. Sprague--Dawley rat pups (P7) were injected intraperitoneally with NaCl or 4 mg/kg/BW lipopolysaccharide (LPS) and then sacrificed at 2, 4, 24, and 48 hr. Sepsis syndrome was confirmed by elevated serum tumor necrosis factor (24.6 ng/mL +- 18.4 [LPS] and &lt 1.0 ng/mL [controls] p &lt .05). Proteolysis in gastrocnemius/soleus muscle was analyzed by quantitation of tissue tyrosine loss. The neonatal rats injected with LPS had significant media tyrosine release at 24 hr compared to the controls (0.39 +- 0.14 versus 0.25 +- 0.11 umol tyrosine/g muscle p &lt .05). At 48 hr, LPS-induced muscle tyrosine release ceased (0.24 +- 0.04 [control] versus 0.23 +- 0.03 umol tyrosine/g muscle [LPS]). After 48 hr, gastrocnemium/soleus weight was less in the LPS-injected rats (50.5 +- 4.8 to 31.2 +- 4.0 g p &lt .0001). Similar changes were not seen in the extensor digitorum longus, suggesting that some muscles were relatively preserved. Also, LPS resulted in significant weight loss. We conclude that selective muscle proteolysis contributes to nitrogen loss in neonatal sepsis. Although proteolysis abates by 48 hr, short-term injury results in significant muscle-mass deficit. Author Affiliation: (1) Department of Pediatrics, Divisions of Gastroenterology and Neonatology, University of Minnesota, Minneapolis, MN (2) Children's Hospital--St. Paul, MN (3) Department of Pediatrics, The University of Minnesota, Mayo Mail Code 185, Minneapolis, MN, 55455 Article History: Registration Date: 12/10/2004

Women drug addicts who are IHV-positive may lose weight despite an adequate diet. This was the conclusion of a study of 39 current drug users, 103 past users, and 61 non-users, all of whom were HIV-positive.

Byline: Luiz G. Santoro (1), George Grant (2), Arpad Pusztai (2) Keywords: Digestibility; Nitrogen secretion; Phaseolin; Small intestine composition Abstract: Rats fed a diet containing a highly purified preparation of phaseolin, the main globulin from the seeds of Phaseolus vulgaris, rapidly lost weight. Fecal nitrogen outputs were elevated and the N digestibility, based on conventional method estimation, was only 37.5%. By using immunological techniques, however, it was shown that the bulk of the nitrogen recovered in the feces was not chemically related to phaseolin. After correction for this non-phaseolin N, the true digestibility of phaseolin was estimated to be 74.3%. It is suggested that phaseolin and/or undigested fragments derived from the native molecule may, as reported for the lectins, stimulate the secretion of endogenous N, possibly mucins. Author Affiliation: (1) Depto. Fisiologia Vegetal, CEP 13083, Campinas, SP CP 6109, Brasil (2) The Rowett Research Institute, Greenburn Rd., AB2 9SB, Aberdeen, Scotland Article History: Registration Date: 13/10/2004

Severe weight loss among men with HIV infection may be caused by a decrease in the amount of food energy taken in rather than an increase in the rate of use of stored energy. Doctors studied the energy use and food intake of 27 HIV-positive men during periods of weight gain and rapid weight loss to determine the factors leading to the rapid changes in weight during HIV infection. Among the patients, the average daily energy use was about 2750 calories (kcal) per day. This energy output was not significantly different from that of healthy men in the same age range. However, during periods of weight loss, the patients average total energy output decreased to about 2180 kcal/day because of reduced physical activity and decreased appetite associated with illnesses or side effects of drug therapy. The patients who were losing weight rapidly had the lowest level of total energy output, while those with a stable weight or a gain had the highest level.

Forty-four intact, male lambs (20 Timahdit and 24 D'man) were used to assess the effects Of 22% (from approximately 25 to approximately 20 kg) and 31% (from approximately 25 to approximately 17 kg) live weight loss and the subsequent refeeding to initial BW on changes in body components. Body composition was determined using a serial slaughter technique at 17, 20, and 25 kg live weight during normal growth, weight loss, and refeeding phases. Reduction in live weight from 25 to 20 kg was associated with greater loss of visceral organs (30%) and internal fat (75%) than carcass loss (19%). Further body weight loss (from 20 to 17 kg) involved carcasses to a greater extent than internal organs. The composition of BW loss consisted of 53% water, 28% fat, and 15% protein. Refeeding was associated with a rapid increase in organ weights and less fat regeneration. Although total internal organs recovered only 90% of their original weight, liver and kidneys regained all their weight. At the same slaughter weight, carcass and noncarcass components of refed lambs were leaner because of lower fat content in these components. Key Words: Lambs, Underfeeding, Refeeding, Carcass Composition J. Anim. Sci. 1992. 70:2859-2865, A study on Moroccan lambs indicated that loss in weight of metabollically active organs, such as liver and kidney, accounts for most of the weight loss during undernutrition. Forty-four lambs were fed with restricted diet to determine the alteration in weight of internal organs and assess the changes in carcass and noncarcass components at pre-determined stages of weight loss. Gain in weight under conditions of ad libitum access to feed was also assessed. At identical slaughter weight, refed lambs had lower fat content in the carcass and noncarcass component than lambs in the control group.