Life Extension Magazine

Life Extension Magazine April 2007

Abstracts

Weight Loss

Emotional influences on food choice: sensory, physiological and psychological pathways.

Sensory, physiological and psychological mechanisms are reviewed that underlie emotional influences on food choice. Both moods and emotions are considered. Eating a meal will reliably alter mood and emotional predisposition, typically reducing arousal and irritability, and increasing calmness and positive affect. However, this depends on the meal size and composition being close to the eater’s habit, expectations and needs. Unusual meals—e.g. too small, unhealthy—may negatively affect mood. Sweetness, and sensory cues to high energy density, such as fatty texture, can improve mood and mitigate effects of stress via brain opioidergic and dopaminergic neurotransmission. However, adaptation in these pathways, perhaps enhanced by inherited sensitivity, with chronic exposure to such sensory qualities, could lead to overeating of energy-dense foods and consequent obesity. Sweet, fatty foods low in protein may also provide alleviation from stress in vulnerable people via enhanced function of the serotonergic system. Moreover, in rats, such foods seem to act as part of a feedback loop, via release of glucocorticoid hormones and insulin, to restrain activity of the hypothalamic pituitary adrenal axis during stress. However, this effect is also associated with abdominal obesity. In humans, a number of psychological characteristics predict the tendency to choose such foods when stressed, such as restrained or emotional eating, neuroticism, depression and premenstrual dysphoria, all of which could indicate neurophysiological sensitivity to reinforcing effects of such foods. Greater understanding of such predictive traits and the underlying mechanisms could lead to tailoring of diet to meet personal emotional needs.

Physiol Behav. 2006 Aug 30;89(1):53-61

Keynote review: phosphodiesterase-4 as a therapeutic target.

Cyclic AMP (cAMP) is a key second messenger in all cells. It is compartmentalized within cells and its levels are controlled, as a result of spatially discrete signaling cassettes controlling its generation, detection and degradation. Underpinning compartmentalized cAMP signaling are approximately 20 members of the phosphodiesterase-4 (PDE4) family. The selective inhibition of this family generates profound, functional effects and PDE4 inhibitors are currently under development to provide potential, novel therapeutics for the treatment of inflammatory diseases, such as asthma, chronic obstructive pulmonary disease and psoriasis, as well as treating depression and serving as cognitive enhancers. Here, we delineate the range of PDE4 isoforms, their role in signaling, their structural biology and related preclinical and clinical pharmacology.

Drug Discov Today. 2005 Nov 15;10(22):1503-19

Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men.

There is evidence that CCK and glucagon-like peptide-1 (GLP-1) mediate the effects of nutrients on appetite and gastrointestinal function and that their interaction may be synergistic. We hypothesized that intravenous CCK-8 and GLP-1 would have synergistic effects on appetite, energy intake, and antropyloroduodenal (APD) motility. Nine healthy males (age 22 +/- 1 yr) were studied on four separate days in a double-blind, randomized fashion. Appetite and APD pressures were measured during 150-min intravenous infusions of 1) isotonic saline (control), 2) CCK-8 (1.8 pmol.kg(-1).min(-1)), 3) GLP-1 (0.9 pmol.kg(-1).min(-1)), or 4) both CCK-8 (1.8 pmol.kg(-1).min(-1)) and GLP-1 (0.9 pmol.kg(-1).min(-1)). At 120 min, energy intake at a buffet meal was quantified. CCK-8, but not GLP-1, increased fullness, decreased desire to eat and subsequent energy intake, and increased the number and amplitude of isolated pyloric pressure waves and basal pyloric pressure (P < 0.05). Both CCK-8 and GLP-1 decreased the number of antral and duodenal pressure waves (PWs) (P < 0.05), and CCK-8+GLP-1 decreased the number of duodenal PWs more than either CCK-8 or GLP-1 alone (P < 0.02). This was not the case for appetite or isolated pyloric PWs. In conclusion, at the doses evaluated, exogenously administered CCK-8 and GLP-1 had discrepant effects on appetite, energy intake, and APD pressures, and the effects of CCK-8+GLP-1, in combination, did not exceed the sum of the effects of CCK-8 and GLP-1, providing no evidence of synergism.

Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1477-85

Interaction between GLP-1 and CCK-33 in inhibiting food intake and appetite in men.

Glucagon-like peptide-1 (GLP-1) and CCK-33 were intravenously infused alone or in combination into normal weight men for 60 min before they were served a lunch of ham sandwiches, chocolate mousse, and orange juice. Infusion of GLP-1 (dose: 0.9 pmol x kg(-1) x min(-1)) or CCK-33 (dose: 0.2 pmol x kg(-1) x min(-1)) each reduced calorie intake of the test meal. However, simultaneous infusion of these peptide doses reduced calorie intake less than the sum of the peptides’ individual effects. Infusions of the same doses of GLP-1 plus CCK-33 had neither individual nor interactive effects on meal size or calorie consumption. The combination of GLP-1 plus CCK-33 induced, however, a significant reduction in hunger feelings in the premeal period (P = 0.036 vs. all other treatments). In summary, intravenous infusion of near physiological doses of CCK-33 and GLP-1 produced specific inhibitions of hunger feeling in men; the simultaneous infusion resulted in an infra-additive reduction in calorie consumption, rejecting thereby the hypothesis that the two peptides exert a positive synergistic effect on food intake compared with the effects observed with infusion of individual peptides. In conclusion, CCK and GLP-1 are meal-related satiety signals that are released from the gastrointestinal tract during food intake.

Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R562-7

Glucagon-like peptide-1 in the pathogenesis of obesity.

The recently discovered gut peptide glucagon-like peptide-1 (GLP-1) is one of many peptides implicated in the short-term regulation of appetite. GLP-1 is a 30-amino-acid peptide that is produced in and secreted from the L cells of the intestinal mucosa after intake of a mixed meal. The amino acid sequence of GLP-1 is highly conserved and all mammals studied to date have identical GLP-1 sequences. GLP-1 receptors have been found in the lung and stomach, and binding of GLP-1 to skeletal muscle and fat cells has been demonstrated. At physiological plasma levels GLP-1 inhibits meal- and pentagastrin-induced gastric acid secretion. In addition, gastric emptying is delayed. Plasma GLP-1 is acutely elevated in normal-weight subjects after a meal, but obese subjects seem to have an attenuated GLP-1 release in response to meals. Consequently, GLP-1 may be a candidate for meal termination and intermeal satiety by either peripheral or central pathways. In terms of the importance of GLP-1 in the pathogenesis of obesity, research points in the direction of a vicious circle where overfeeding results in a down-regulation of postprandial GLP-1 release, which may result in the consumption of a larger amount of calories to elicit a “normal” GLP-1 satiety signal, thus perpetuating the obese state.

Drug News Perspect. 1998 Mar;11(2):92-7

Ice-cream consumption, tendency toward overeating, and personality.

OBJECTIVE: The exploration of the mechanisms underlying the tendency toward overeating by investigating the Dutch Eating Behavior Questionnaire (DEBQ)/Revised Eating Disorders Inventory (EDI-R) disinhibition, in sequence to the milkshake-ice cream study (van Strien, Cleven, and Schippers, in press). METHOD: In hierarchical multiple regression analyses, the relative predictive power for ice-cream consumption was assessed, that is, emotional versus external versus bulimic eating using scales of the DEBQ and the EDI-R. In nonplanned stepwise multiple regression analyses, the association was assessed between these three types of eating behaviors and non-eating-related EDI-R scales. RESULTS: Emotional eating was the most important variable for ice-cream consumption. External eating was borderline significant and bulimic eating nonsignificant when emotional and external eating had been partialled out. Emotional eating was best predicted by the EDI-R scales Asceticism, Interoceptive Awareness, and Social Insecurity. DISCUSSION: Results are consistent with psychosomatic theory, which focuses on emotional eating as the result of confusion and apprehension in recognizing and accurately responding to emotional and visceral states related to hunger and satiety.

Int J Eat Disord. 2000 Dec;28(4):460-4

The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain.

Objective:The incidence of obesity and overweight in the US has increased considerably during the past two decades and currently affects 65% of the adult population. Research has indicated that small, yet irreversible, gains during the holiday season contribute to increases in weight during adulthood. Conjugated linoleic acid (CLA), a naturally occurring dietary fatty acid, has been found to reduce weight gain and dramatically decrease fat mass in animals. Although research in humans has shown inconsistent results, most studies have been of insufficient duration or have utilized body composition methods that are less accurate than the currently accepted criterion.Design:Randomized, double-blind, placebo-controlled study of 3.2 g/day CLA for 6 months.Subjects:Forty healthy, overweight subjects (age: 18-44 years; body mass index: 25-30 kg/m(2))Measurements:Body composition by the four-compartment model, resting metabolic rate (RMR) by indirect calorimetry, self-reported physical activity and dietary intake, and blood chemistries were determined at baseline and after 6 months. Body weight was measured monthly during the pre-holiday season (August-October), holiday season (November-December) and post-holiday season (January-March). Adverse events were assessed monthly.Results:Compared to CLA, the placebo group showed a greater rate of weight gain during the holiday season (P=0.01). Within the placebo group, holiday weight change was significantly greater compared to the pre-holiday period (August-October) (P=0.03). Six-month change in body composition was improved with CLA compared to placebo (P=0.02), and body fat was significantly reduced within the CLA group (-1.0+/-2.2 kg, P=0.05). CLA had no effect on RMR, physical activity or dietary intake. The rate of reported negative emotions decreased significantly with CLA, although there was no difference in any other category of adverse event. In comparison to the placebo, CLA did not affect insulin resistance, blood lipids and markers of liver function or markers of inflammation, with the exception of a significant decrease in a biomarker of endothelial dysfunction.Conclusion: CLA supplementation among overweight adults significantly reduced body fat over 6 months and prevented weight gain during the holiday season. Although no adverse effects were seen, additional studies should evaluate the effect of prolonged use of CLA.

Int J Obes (Lond). 2006 Aug 22

The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes.

Conjugated linoleic acids (CLA) are a group of positional and geometric conjugated dienoic isomers of linoleic acid. The objective of this study was to determine the effects of the cis-9,trans-11 and trans-10,cis-12 isomers of conjugated linoleic acid on lipid composition and gene expression during the differentiation of mouse 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 preadipocytes with trans-10,cis-12 conjugated linoleic acid (CLA) resulted in a dose-dependent decrease in the expression of the stearoyl-CoA desaturase 1 gene (SCD1). The expression of other adipocyte genes such as adipose P2 (aP2), fatty acid synthase (FAS), SCD2 and the key adipogenic transcription factors, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT enhancer binding protein alpha (C/EBPalpha), remained elevated. Cells treated with trans-10,cis-12 CLA exhibited smaller lipid droplets, with reduced levels of the major monounsaturated fatty acids, palmitoleate and oleate. By contrast, the cis-9,trans-11 isomer did not alter adipocyte gene expression. Repression of the stearoyl-CoA desaturase gene expression in adipocytes by the trans-10,cis-12 isomer may contribute to the mechanisms by which CLA reduces body fat in mice.

J Nutr. 2000 Aug;130(8):1920-4

Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects.

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects on body-weight maintenance, parameters of appetite and energy intake (EI) at breakfast after weight loss. DESIGN: This study had a double-blind, placebo-controlled randomized design. SUBJECTS: A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index 27.8+/-1.5 kg/m(2)). INTERVENTIONS: Subjects were first submitted to a very-low-calorie diet (VLCD; 2.1 MJ/day) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day or 3.6 g CLA or placebo per day. Additionally, subjects of the high dosage intervention replaced their habitual lunch by one meal of a protein-rich, low-energy supplement. EI was measured at breakfast and appetite profile after an overnight fast. RESULTS: The mean body weight loss was 6.9+/-1.7% of their original body weight. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not have an effect on body weight regain. Feelings of fullness and satiety were increased and feelings of hunger were decreased after 13 weeks intervention by CLA compared to placebo, independent of %body weight regain. However, EI measured at breakfast was not affected by CLA. CONCLUSION: Appetite (hunger, satiety and fullness) was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day. This did not result in a lower EI at breakfast or an improved body-weight maintenance after weight loss.

Eur J Clin Nutr. 2003 Oct;57(10):1268-74