One day of moderate overfeeding (30% excess energy intake) already increases the hepatic insulin resistance index. Fat accumulation in the liver (not related to alcohol, viral infection or liver diseases) is associated with obesity, insulin resistance, diabetes and alteration of lipid profiles, oxidative stress, mitochondrial dysfunction and inflammation. Weight loss significantly improves fasting flow-mediated vasodilation of the brachial artery in adults (a measurement of endothelial function). A meta-analysis of 20 studies involving 1259 participants indicated that weightloss (mean 8% of initial bodyweight) improves pulse wave velocity (a measure of arterial stiffness).
Though exercise increases insulin sensitivity (preventing insulin resistance), calorie restriction does the same, through autophagy. This is regardless of whether this restricted diet is moderate-carbohydrate (40-45% of energy) and increased-protein (25-30%), or high-carbohydrate diet (55-60%) and moderate-protein (15%). A low-calorie diet significantly improves the Heart Rate Recovery after maximum exercise, predicting cardiovascular disease risk and mortality.
A systematic review of 49 high-quality scientific studies shows that there is little evidence to indicate that men and women should adopt different weight loss strategies , though appetitive response to external cues as an important risk factor in appetite control is mediated through cravings for particular food groups and is gender-dependent. In the United States, women are approximately twofold more vulnerable to severe and morbid obesity. In both the USA and Spain, women crave sweet foods most frequently, whereas men crave mainly savory foods. Chocolate is the single most craved food among women, with a maximum in the late luteal and menses phase. Women empty both solids and liquids from the stomach significantly more slowly than men. Total daily energy intake in male rats exceeds that in females to an extent greater than predicted by their larger lean body mass and metabolic rate. This higher normal “homeostatic” eating contributes to the maintenance of more body fat in females. Dieting is associated with more pronounced alterations in postsynaptic serotonin activity in women than in men. In response to fasting, women tend to eat less than men. Women decreased their food intake after fasting as their eating pattern became more linear (eating at a nearly constant rate). Linear eating, and the dieting that elicits linear eating, is part of the pattern that characterizes patients with anorexia nervosa. The lifetime prevalence of psychiatric eating disorders  and various symptoms of disordered eating  are about three-fold higher in women than in men.
Females are slower to recover (and some aspects do not recover at all) from a high-fat diet-induced change in the dopamine reward system. Additionally, the rate of serotonin synthesis is 52% greater in males than in females , in females serotonin is metabolized more rapidly , and are women more susceptible to the influence of lowered availability of tryptophan (for serotonin synthesis). Also, the behavioral response to sucrose is more strongly associated with changes in opioids. Ghrelin levels are positively associated with testosterone levels in men and estrogen levels in women. 17 alpha-estradiol (as a neuro-estrogen) influences appetite in the brain  and eating, fluid intake and food hoarding vary rhythmically during the estrous cycle. Estrogens indirectly activate Gonadotropin-releasing hormone (GnRH). Gonadatropin-inhibitory peptide is involved in the negative feedback effects of estrogens and acts a functional antagonist to GnRH. Gonadatropin-inhibitory peptide directly influences appetite. Women may eat more sweet foods during the luteal phase than during the mid-follicular phase  The difference in energy intake between the follicular and luteal phases may vary from ∼10% to ∼23%.
In general, self-efficacy regarding macro-nutrients intake is moderate. Intensive nursing strategies for increasing self-efficacy for weight control and health-promoting behaviour may be essential components for better weight loss in the initial stage of a weight management intervention. Particularly increases in diet self-efficacy had a significant indirect effect on initial weight loss. Obese men and women tend to under-report their energy intake  and resort to irregular eating between meals. People given larger portions consumed 30% more than those given smaller portions. People cannot accurately estimate the calories in various food items and underestimate calories depending on the context in which the foods are presented. A typical restaurant meal may provide 2 to 5 times more calories than needed. BMI positively predictes self-selected portion size, and people chose larger portion sizes for high-carbohydrate foods when compared to high-fat foods. People have no internal cues allowing them to regulate precisely the number of calories they consume. People tend to consume more during a meal when there are more people sitting at a table. Gastric emptying of solids and change in gastric volume with ingestion of a standard meal do not appear to determine the change in satiation.
Individuals vary in their responsivity to cues that motivate overeating. Those higher in responsivity need specialized self-regulatory skills. These skills include an ability to tolerate uncomfortable internal reactions to triggers and a reduction of pleasure, behavioral commitment to clearly-defined values, and metacognitive awareness of decision-making processes. Such acceptance-based interventions based on these skills have so far proven efficacious for weight control, especially for those who are the most susceptible to eating in response to internal and external cues. Subjects that readily loose most weight, have higher responsive fatty acid levels, and lower changes in leptin and insulin concentrations, suggesting a better metabolic flexibility. To reduce compensatory responses one needs to account for individual activity level before prescribing weight-loss program associating diet and exercise. Energy intake may increase as the inter-meal interval increases. Meal-skipping is associated with compensatory eating, higher energy intake per eating occasion and increased visceral adipose tissue. Step counts (10.000/day) may be a key area to target. Problem solving is another key component. Successfully achieving the target weight loss in a comprehensive program predicts subsequent maintenance of lower weight without increasing the risk of dropout. Providing the additional strategies at predetermined times over the intervention period enhances weight loss.
PYY released from the gut induces satiety, in response to the inflow of nutrients. Short-term appetite regulating hormones such as PYY similarly regulate reward and craving for drugs and cigarettes. Duodenal lipid more profoundly than protein stimulates plasma PYY.  Protein increases PYY more than maltodextrin (absorbed as glucose). High protein diets increases PYY more than high carbohydrate diets. Meat stimulates PYY more so than a vegan meal does. Slow spaced eating does not affect PYY levels. Constitutional thinness is associated with high PYY (peptide tyrosine tyrosine; secreted by intestinal cells ) in circadian profile. Similarly, PYY may be elevated in anorexia nervosa , or totally the opposite. Mean PYY levels are lower in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa. High PYY may represent a protective response against significant weight gain. PYY levels are positively (or negatively) associated with disordered eating psychopathology including restraint and eating concerns, independent of body mass index (BMI). Short-term aerobic exercise does not affect PYY levels. Interval exercise (rope skipping exercise (295 kcal, 3 sets × 10 min with 5-min interval or bicycle ergometer exercise (288 kcal, 3 sets × 10 min with 5-min interval, followed by 2 hours resting) did increase PYY. Endurance exercise increases PYY more, and eventual relative energy intake was lower in comparison with interval exercise.
Leptin is a long-term regulator of energy balance. Plasma leptin levels are tightly correlated with body fat mass, signalling adiposity status to the brain, initiating compensatory changes in eating and energy expenditure, especially in the case of reduced adiposity. Basal plasma leptin levels are linearly related to fat mass. Leptin regulates appetite by inhibiting serotonin synthesis. Neither intraduodenal lipid nor protein affects plasma leptin. In anorexia nervosa, leptin levels after a meal are lower. Mean leptin levels are lower in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa. Leptin levels are not significantly associated with disordered eating psychopathology.
Ghrelin (stimulating appetite) is involved in short-term regulation. Ghrelin represents 'stomach hunger', as released from the stomach, signalling hunger to the brain. Ghrelin increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Ghrelin levels are not significantly associated with disordered eating psychopathology, including restraint and eating concerns , but may be positively associated to restrictive eating. Ghrelin is similarly suppressed by lipid and protein. Meat suppresses ghrelin more so than a vegan meal does. Slow spaced eating does not affect ghrelin levels. Acute exercise (on a cycle ergometer at 70% until 30% of total daily energy expenditure) did not affect the appetite hormones, but did suppress appetite. Ghrelin levels are positively associated with estrogen levels in women.
Soluble fiber may be bacterially decomposed in the intestines through fermentation (yielding gasses). Polydextrose (a water-soluble fiber) does not affect Ghrelin or PYY. Cellulose (10% w/w; water-insoluble) also does not, but the water-soluble fibers beta-glucan (in cereals and bran), and particularly fructo-oligosaccharide and pectin (both present in fruits and vegetables) (all 10% w/w) increase PYY levels 2.3-, 3.1- and 3.0-fold respectively, and decrease bodyfat. A 5% dietary fiber content is insufficient to elicit these effects. The greatest sources of pectin are: dried apricot (5%), cooked white beans (<2%), apricot (1%), plum and strawberry (0.8%), kiwi [0.7), banana (0.6%), kaki and peach (0.5%), and OJ (0.09%)  apples (1-1.5%), carrots (1.4%) and oranges (0.5-3.5%).  The three effective soluble fibers are mainly decomposed into succinate, by the Bacteroides and Clostridium genera. High nitrogen (from high-quality protein) relative to carbohydrate fosters succinate formation. It is unlikely that the increased succinate per se elicits the satiety response , as short-chain fatty acids do not play a role in appetite regulation. Fiber in general may contribute to weight gain through improved energy extraction from diet by the conversion of dietary fibre to short-chain fatty acids, such as propionic acid and acetic acid, substrates for de novo lipogenesis and gluconeogenesis , though propionic acid (10 g/day) stimules PYY release.
Oxytocin may also be involved in the pathophysiology of anorexia nervosa. Oxytocin regulates nonhomeostatic, reward-related food intake. Oxytocin attenuates the attentional vigilance to eating. The oxytocin system may be deranged in anorexia nervosa. Differential regulation of the oxytocin receptor gene in anorexia nervosa is shown by elevated methylation levels at five sites. Abnormal oxytocin secretion after eating a meal in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. In anorexia patients, oxytocin levels are elevated after a meal (and lower than normal in recovered anorexia patients), and associated with the severity of disordered eating psychopathology. The effects of oxytocin may last as long as 4 hours. In Prader-Willi syndrome, a condition involving insatiable hunger, the inbitory actions of oxytocin on appetite may be absent. Basal  and overnight secretion of oxytocin in women with anorexia nervosa is decreased compared with healthy women. This may partly be due to lower serum activity of prolyl endopeptidase  and/or elevated levels of autoantibodies reacting oxytocin in anorexia nervosa, associated with severity of the disease. Phenylethylamine (in chocolate , metabolised mainly to phenylacetic acid ) may stimulate dopamine levels , which is strongly associated with the reward system. Dopamine in the nucleus accumbens may activate oxytocinergic neurons. Chocolate also contains dopamine, histamine, serotonin  theobromine and caffeine. Catecholamines such as dopamine stimulate the breakdown of bodyfat into triglycerides and glycerol. Dietary serotonin increases serum 5-HIAA (the main serotonin metabolite) within 2 hours, and 5-HIAA concentration returns to baseline concentration within 24 hours.
Fat + Carbohydrates
Weight changes after a 5 year follow up in 373.803 Europeans revealed that a higher proportion of energy from protein at the expense of fat or carbohydrates is positively associated with weight gain. Meat intake may predict BMI standard deviation score. Statistical analysis of the data for 38.409 individuals, showed that the consumption of sugar-sweetened beverage alone is not associated with obesity risk. Total energy intake is the primary contributor to body mass index in all age groups. Sugar intake does not predict daily energy intake, nor body mass index. In households with an overweight child, grains supplied significantly more protein and carbohydrate than in comparison households. Overall carbohydrate intake is negatively associated and fat intake is positively associated with body mass index. People with >30 % fat contribution to daily energy intake are at reduced odds of being overweight/obese. Dietary fat and carbohydrates have differential 'rewarding' pathways. Hence one does not inhibit the appetite for the other. And its particularly the combination of high-fat plus high-sugar foods that makes children grow bigger , such as fast-food plus sweetened beverages.
When people are shown a picture of food, they secrete dopamine in the dorsal striatum, which results in cravings and motivations to eat. People are born with natural preferences for sweets. People also prefer fats because they too activate the brain's reward system. Acutely, palatable food causes a burst of dopamine in the central reward system. With chronic consumption of rewarding food, the increased dopamine release over time may lead to adaptations that are associated with reward hypo-function.
The acquisition of hedonic feeding appears to involve activation of the mesolimbic dopamine system. Several neurotransmitter (eg serotonin ) and neuropeptide systems (including ghrelin , leptin , cannabinoids , opioids ) that modulate feeding do so, at least in part, by acting through the mesolimbic dopamine pathway. When food is restricted, the dopamine response (and the acetylcholine satiety effect } to palatable food is correlated with the amount of food consumed, and the magnitude of the increase in dopamine is enhanced by previous food deprivation. Dopamine response to palatable foods decreases following repeated exposure. (after chronic high-fat diet , and in obese humans, the dopamine response to palatble foods is blunted.) However, this does not appear to be the case when intermittently food-restricted. Decreased dopamine signaling reduces the sensitivity to natural rewards and may therefore facilitate continued overconsumption of palatable foods and further weight gain. These effects may persist after a short withdrawal period , but may reverse after a longer period of weight loss. Tyrosine hydroxylase is subject to feedback inhibition by catecholamines (eg epinephrine, norepinephrine, dopamine). Brain tyrosine (precursor for dopamine) corresponds with homovanillic acid levels (metabolite associated with dopamine levels). Serotonin turnover interacts with dopamine turnover , but while dopamine transmission is constrained by synthesis and repackaging, serotonin transmission is mostly sensitive to uptake and metabolic degradation mechanisms.
Serotonin is a hormone when made in the gut  and a neurotransmitter when made in the brain. Serotonin acts at many receptor subtypes throughout the brain, and its actions in reward are receptor subtype-dependent. Serotonin may reduce caloric intake, an effect associated with reduced hunger and increased satiety. Augmentation of brain serotonin inhibits food intake, while depletion of brain serotonin promotes weight gain. Manipulations that increase serotonin neurotransmission (including the administration of tryptophan) lead to reduced eating behaviour, whereas those that reduce serotonin activity precipitate compulsive or binge eating. Anorexia nervosa may correspond to a primary state of increased serotonin tone. Tryptophan is the precursor for serotonin (and vitamin B3 ). Relative tryptophan depletion may increase impulsivity. Tryptophan-depletion paradigms that use dietary manipulations to lower brain tryptophan and serotonin synthesis have been shown to exacerbate bulimic symptoms in patients with active bulimia nervosa. Dieting is known to produce reductions in tryptophan availability and in the ratio of tryptophan to total large neutral amino acids. Dieting in women is associated with the development of functional supersensitivity of serotonin receptors, probably in response to lowered levels of brain serotonin. In addition, phenylalanine inhibits decarboxylation of 5-hydroxy-L-tryptophan (into serotonin) and leucine enhances tryptophan-pyrrolase. Moreover, several amino acids all compete for the same blood-brain barrier carrier system: phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophane, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine , though the effects of inhibition of tryptophan uptake into the brain are small in comparison to the effects of lowering of tryptophan levels. A 100 g mixture of 15 amino acids lowered plasma tryptophan in healthy men by 76% and caused a lowering of mood. Large neutral amino acids reduce tryptophan uptake into human brain.
The mean tryptophan/protein content in the human body is 1.2%. The tryptophan/protein content is 7.4% in dried Edible boletus, 5.8% in fresh Edible boletus, 2.6% in dried dates, 1.8% in chicken egg yolk and in strawberries, 1.6% in hazelnuts and in banana. The requirement of protein for healthy Japanese females is approximately (≈) 50 g/day. So that ≈0.6 g of tryptophan is supplied from daily meals and is also catabolized daily by the body , which is the amount of tryptophan in 41 grams of dried Edible boletus, in 207 grams of chicken egg yolk, 300 grams of hazelnuts, 1.2 kg of dried dates or 3.3 kg of banana.) The rate of synthesis of melatonin (and sleep ) also depends on tryptophan availability.
Agonists of all three opioid receptor subtypes in the brain, μ, δ, and κ, increase food intake . More specifically, manipulations of the opioid system regulate hedonic feeding or the intake and response to highly palatable macronutrients (high-fat and/or high-sucrose) . Manipulations that increase dopamine levels also enhance preference for and real intake of sucrose. Stimulation of opioid receptors increases dopamine release. β-casomorphins (from milk products) are a family that has shown μ-opioid receptor agonist activity. Wheat-opioid peptides (in gluten: gliadins and glutenins) also survive gastric digestion and increase intestinal permeability. Such exorphins may not directly regulate the ingestion of carbohydrates.
The analysis of 119 scientific publications in participation with ten medical specialty societies resulted in the recommendation that for the purpose of weightloss and stabilization of a lower weight, a diet with an energy deficit of 500 kcal/day and a low energy density should be instituted. When calories were reduced by an average of 422 kcal/day for 12 weeks, body fat mass was reduced by 10.2%, and waist circumference by 5%, while insulin sensitivity improved significantly. Menstrual disturbances are associated with energy deficits over 470 kcal / day. Negative-calorie diets ("containing less energy than required for its digestion") and low-calorie diets are equally efficacious regarding weightloss. There is probably little or no difference in weight loss up to two years of follow-up when overweight and obese adults are randomised to low carbohydrate and isoenergetic balanced weight loss diets.
Adherence to any diet may result in weight loss, regardless of whether low in carbohydrates or low in fat. A healthy low-energy diet leads to sustained weight loss, regardless of an emphasis on more vegetables. Among overweight/obese adults, participants who consumed the lower-carbohydrate diet lost more intra-abdominal adipose tissue than participants on the low-fat diet. Relative weight loss may be 7.4% for a low-fat diet versus 9.0% for the low carb version. A Palaeolithic-type diet had similar long-term effects on body weight and metabolic balance in comparison with a diet in accordance with the Nordic Nutrition Recommendations. Very-low-energy diets (below 600 kcal/day) and ketogenic low-carbohydrate diets are associated with a suppression of appetite, despite weightloss. Weight loss in Very-Low-Carb (4% of energy vs 35% protein, 61% fat) and High Carb diets (46% of energy vs 24% protein, 30% fat) was similar during 1 year. Medium chain triglycerides suppress appetite more than long-chain triglycerides do, independent of hormone levels (incl. PYY). In women, poly-unsaturated and saturated fatty acids elicit a stronger satiety response (based on PYY levels) compared to mono-unsaturated fatty acids. In children, obesity and PUFA intake may be inversely associated. Including 50 g of almonds daily in the diet led to a greater weight-loss.
High dietary fat intake leads to insulin resistance in skeletal muscle by increasing the H2O2 (ROS radical) emission of mitochondria.. Acute nutrient deprivation also increases ROS , contrasting to the effect of constitutive nutrient deprivation (calorie restricted diet). ROS production in mitochondria is nutrient-sensitizing (similar to autophagy) . Thus the differences in constitutive and acute stress-induced autophagy may result from differential ROS levels in skeletal muscle.
Intermittent fasting involves restricting energy intake on 1-3 days per week, and eating freely on the nonrestriction days , which appears to be an effective strategy for weight loss. Waist circumference, percentage fat mass, and fat mass decreased significantly and similarly in women taking an intermittent diet and women taking a continuous diet. Analysis showed that intermittent fasting and continuous energy restriction are equally effective for weight loss. Results reveal similar weight loss and fat mass loss, but less fat free mass was lost in response to intermittent fasting versus daily calorie restriction, with 3 to 12 weeks of restriction.
Alternate-day fasting (25% energy intake alternated with ad libitum) diet decreases body weight, BMI and fat mass, regardless of whether the diet is high (40%) or moderately low in fat (25%). Alternate day fasting (24 hours of feeding alternated with 24 hours of consuming 25% of normal energy intake, at lunchtime) produces similar weight loss and cardio-protection as consuming the meal at dinner, or dividing that 25% energy intake in smaller meals. Results reveal superior decreases in body weight by calorie restriction versus intermittent or alternate day fasting regimens, yet comparable reductions in visceral fat mass.
The circadian clock is closely associated with energy metabolism. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Circadian rhythms occur in all species and even in a cell. Disruption of circadian rhythms leads to obesity. Time-restricted feeding (actually a key component of intermittent fasting regimens) allows ad libitum energy intake within controlled time frames, generally a 3-12 hour range each day. Benefits are proportional to the fasting duration. If you don’t eat for 10–16 hours, your body will go to its fat stores for energy.  Time-restricted feeding, in which feeding is consolidated to the nocturnal phase, partially restores the highly dynamic daily cyclical fluctuations in gut microbiome composition. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora. Even without reducing caloric intake, and even when high in fat, if time-restricted fed, this may protect against obesity.
Endurance training per se increases peak fat oxidation during exercise. Combining caffeine with exercise creates a greater acute energy deficit. Caffeine also leads to exercise being perceived as less difficult and more enjoyable.
Aerobic exercise training in women typically results in minimal fat loss / reductions in bodyweight. Exercise interventions (55-64%) more than than diet interventions (12-44%) tend to trigger behavioral compensation (resulting in less weight loss). 75% of subjects self-report to engage in compensatory eating in response to exercise, for reward, relief and recovery. Meta-analyses of 45 scientific trials involving 7788 individuals revealed that interventions that deal with both diet and physical activity show small benefits on weight loss. A quantitative analysis of 21 scientific trials (including 3521 participants), revealed that comparing exercise versus diet, diet resulted in a significantly more pronounced decrease in body weight. Diet plus exercise, in comparison to diet alone, reduced total fat, but did not result in a reduction in waist circumference.  As compared to diet restriction alone (energy content based on 70% of measured resting metabolic rate), the addition of strength or aerobic training does not improve changes in BMI, body fat or metabolic risk factors. Dietary restriction with and without exercise result in similar weight loss and no signficant changes in the resting metabolic rate. If not followed up by exercise, low-calorie-induced weight loss will result in a decrease in total energy expenditure and non-training physical activity energy expenditure. (less weight to carry around) Resting energy expenditure will decrease regardless of whether weight loss is follwed up by aerobic or resistance exercise, or not.  The latter may be due to an increase in autophagy. Low physical activity protects lean body mass. Performing aerobic exercise after an overnight fast does not accelerate the loss of body fat, compared to non-fasted exerrcise.
Compared to food restriction alone, the addition of running wheel activity makes mice loose weight faster, but also prevents further weight loss beyond a crucial point of body weight loss (especially fat mass). Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation and a preferential use of glucose in the mice that were also submitted to running wheel activity.
High intensity exercise stimulates compensatory eating. Bikram yoga meets requirements for exercise of light-to-moderate intensity and, theoretically, could be used for weight maintenance or weight loss if practiced several times per week.