Injections of Galanin-Like Peptide directly into the nucleus of the tractus solitarius (NTS) reduces food intake and body weight but increases metabolic rate and plasma leptin.

Galanin-Like Peptide (GALP) is a hypothalamic neuromediator of metabolism and reproduction. GALP is known to stimulate reproduction and alter food intake and body weight in multiple species. The regulation of body weight involves control of both energy intake and energy expenditure. Since GALP is known to alter food intake - possibly via the autonomic nervous system - we first hypothesized that GALP would increase metabolic rate. First, male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannulae and abdominal radiotelemetry temperature transmitters. Following ICV injection with either 5nmol GALP or vehicle, the oxygen consumption of each rat was monitored for 8h. Food intake, core temperature, and general motor activity were monitored for 24h. GALP significantly increased oxygen consumption, an indirect estimator of metabolic rate, without having any significant effect on motor activity. Compared to controls, GALP increased core body temperature during the photophase and reduced food intake over the 24h period following injection. ICV GALP also increased plasma levels of luteinizing hormone (LH). A second group of male Sprague-Dawley rats were implanted with abdominal transmitters and given injections of GALP directly into the nucleus of the tractus solitarius (NTS). These injections resulted in a significant reduction in food intake, and a significant increase in both oxygen consumption and core body temperature compared to vehicle injections. Direct injections of GALP into the NTS compared to vehicle also resulted in a significant increase in plasma leptin levels, but not LH levels. GALP appears to increase energy expenditure in addition to decreasing energy input by actions within the NTS and thus may play an important role in the hypothalamic regulation of body weight.

Anthropometric measures of visceral and subcutaneous fat are important in the determination of metabolic dysregulation in boys and girls at risk for nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is increasing at alarming rates in obese children. The study aim was to describe body composition/somatotype and its interrelationships to biomarkers of liver disease, insulin resistance, and lipid and cytokine expression in youth with NAFLD. METHODS: Somatotype and body composition of children (7-18 years) diagnosed with NAFLD (n= 18) were compared with obese (n = 11) and lean children (n = 17). Anthropometric variables assessed included weight, height, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHTR), and multiple skinfold thicknesses. Fat mass (FM) and somatotype analysis were measured using validated methodologies. Fasting liver biochemistries (aspartate aminotransferase [AST], alanine aminotransferase [ALT], γ-glutamyltransferase [GGT]), insulin, glucose, leptin, C-reactive protein (CRP), tumor necrosis factor-α, interleukin (IL) factors 6/10, apolipoproteins B-100/B-48 and C-III, triglycerides, and high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol were measured. Insulin resistance was assessed by the homeostasis model of insulin resistance (HOMA-IR). RESULTS: BMI z score, WC, FM, and somatotype did not differ between NAFLD and obese groups; however, lean children were lighter/leaner across all anthropometric measures (P < .001). Children with NAFLD had a higher sum-of-trunk to sum-of-extremity ratio (1.6 ± 0.4) than did obese (1.3 ± 0.2) and lean (1.1 ± 0.5) children (P < .001). Markers of central visceral (WC/WHTR) and subcutaneous fat (subscapular, abdominal, suprailiac skinfolds) were associated with elevated plasma concentrations of insulin, HOMA-IR, ALT, GGT, and AST and lower HDL cholesterol and IL-10 (P < .001). CONCLUSION: Comprehensive assessment of body composition, including measurement of surrogate markers of subcutaneous and visceral fat, provides information regarding metabolic dysregulation and liver disease risk in obese children with NAFLD.

A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without nonalcoholic fatty liver disease.

BACKGROUND: Hyperinsulinemia and altered lipid and lipoprotein metabolism induced by fast-food diets may contribute to nonalcoholic fatty liver disease (NAFLD). We hypothesized that a high saturated fat (SFA) meal would evoke prolonged postprandial lipemia and hyperinsulinemia, increased inflammation, and altered lipoprotein expression in obese children with NAFLD when compared with healthy children. METHODS: We prospectively studied 31 children (NAFLD, 13.1 ± 2.6 years, n = 11; age-matched obese, 14.3 ± 1.7 years, n = 9; lean, 13.6 ± 2.6 years, n = 11) following consumption of a high SFA (18.8%) meal. Prior to and at 1, 3, and 6 hours after meal consumption, blood was collected for analysis of alanine aminotransferase (ALT); aspartate aminotransferase (AST); γ-glutamyltransferase; leptin; C-reactive protein; (fasting) insulin; glucose; triglycerides (TGs); total, high-density lipoprotein, and low-density lipoprotein cholesterol; adiponectin; nonesterified fatty acids (NEFAs); inflammatory markers (TNF-α, IL-6, IL-10); apolipoproteins-B48, B100, and CIII; and fatty acid (FA) composition of TG fractions. RESULTS: Children with NAFLD had significantly higher fasting levels of ALT (87 ± 54 U/L), AST (52 ± 33.5 U/L), and apolipoprotein-CIII (20.6 ± 11.3 mg/dL) with postprandial hyperinsulinemia (iAUC insulin: 225 ± 207 [NAFLD] vs 113 ± 73 [obese] vs 47 ± 19.9 [lean] mU/L-h; P < .001); suppression of NEFA (iAUC-NEFA: 1.7 ± 0.9 [NAFLD] vs 0.6 ± 0.3 [obese] vs 1 ± 0.7 [lean] mEq/L-h); and prolonged elevations in apolipoprotein-B48 3-6 hours after meal consumption when compared with obese and lean controls (P < .05). CONCLUSION: A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without NAFLD.