Integrated metabolic control of food intake

doi:10.1016/0361-9230(86)90099-7

Brain Research Bulletin

Volume 17, Issue 6, December 1986, Pages 855-859

https://doi.org/10.1016/0361-9230(86)90099-7 Get rights and content

Abstract

Inhibition of glycolysis and fatty acid oxidation by combined treatment with 2-deoxyglucose (2DG) and methyl palmoxirate, or inhibition of glycolysis and lipolysis by combined treatment with 2DG and nicotonic acid synergistically increased food intake in rats. Methyl palmoxirate treatment alone increased food intake in rats fed a high-fat, but not low-fat diet. These results provide direct evidence for a mechanism in the control of food intake that integrates signals generated by the metabolism of glucose and fatty acids. In addition, they strongly indicate a role for fatty acid oxidation in the control of eating and raise the possibility that an interaction between glucose and fat metabolism underlies the link between regulation of body fat stores and short-term food intake.

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Isoflavones have been identified as potential anti-diabetic agents, but adverse side effects especially at high dosage has continued to plague their clinical uptake. We explore the benefits of individual and co-treatment of diabetic rodents with isoflavone-rich kudzu extract and chaga extract based on effect on glycemic control, regeneration of pancreatic β-cells (immunofluorescence staining assessment of pancreatic insulin and pancreatic and duodenal homeobox 1 (PDX-1) expression), cardiac function (including measurements of left ventricular hemodynamics, and arterial stiffness) and kidney function. Treatment of diabetic rodents with either isoflavone or chaga extract improved glycemic control, enhanced the co-expression of insulin and PDX-1, prevented cardiac hypertrophy, and ameliorated hypercellularity of the glomerulus, expansion of the mesangial matrix and deposition of collagen in kidney tissues. The use of both compounds combined did not provide additional benefits beyond that of each used singly. Further research focusing on exploring the optimal dosage of these combined therapies in experimental diabetes models is highly recommended.
Central and peripheral leptin resistance in obesity and improvements of exercise
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Citation Excerpt :
Furthermore, leptin strongly enhanced the intracellular glucose transporter 4 (GLUT4) transport in muscle of ob/ob mice via decreasing the expressions and activities of two key negative regulators of GLUT4 translocation, Rab-GTPase activating proteins known as Tre-2/BUB2/cdc 1 domain family (TBC1D) 1 and TBC1D4 (also called Akt substrate of 160 kDa, AS160) (Sáinz et al., 2012). It is deserved to mention that an increase in the availability of oxidizable fuels that would result from improved peripheral leptin sensitivity might create a metabolic stimulus to decrease appetite and food intake, given that overeating can be stimulated by blocking the availability of metabolic fuels (Friedman et al., 1986), which might link peripheral and central mechanisms on appetite. Peripheral leptin resistance refers to a loss of leptin's physiological actions that directly occurs in peripheral tissues.
Obesity is strongly related to leptin resistance that refers to the state in which leptin fails to inhibit appetite, enhance energy expenditure and regulate glycolipid metabolism, whereas decreasing leptin resistance is important for obesity treatment. Leptin resistance that develops in brain and also directly in peripheral tissues is considered as central and peripheral leptin resistance, respectively. The mechanism of central leptin resistance is the focus of intensive studies but still not totally clarified. A challenged notion about the effect of impaired leptin BBB transport emerges and a concept of “selective leptin resistance” is discussed. Peripheral leptin resistance, especially leptin resistance in muscle, has drawn more attention recently, while its mechanism remains unclear. Exercise is an effective way to reduce obesity, which is at least in part due to the alleviation of leptin resistance. Here, we summarized newly discovered data about the associated factors of central leptin resistance and peripheral leptin resistance, and the actions of exercise on leptin resistance, which is important to understand the mechanisms of leptin resistance and exercise-induced alleviation of leptin resistance, and to facilitate clinical application of leptin in obesity treatment.
Feed intake is related to changes in plasma nonesterified fatty acid concentration and hepatic acetyl CoA content following feeding in lactating dairy cows
2015, Journal of Dairy Science
Citation Excerpt :
Because late-lactation cows are not in a lipolytic state, their hepatic pool of AcCoA is not expected to be large, and therefore, control of intake in these cows might be less affected by propionate flux to the liver compared with early-lactation cows. Extensive research in laboratory animals supports the theory that oxidation of fuels in the liver affects feed intake (Friedman et al., 1986), and this mechanism has been proposed to be conserved in ruminants (Allen et al., 2005). Fuels that can be extracted from the blood and oxidized in the ruminant liver include propionate, butyrate, NEFA, AA, glycerol, and lactate.
The relationship between hepatic acetyl CoA (AcCoA) content and dry matter intake (DMI) was evaluated using 28 multiparous Holstein cows; 14 were early postpartum (PP; 12.6 ± 3.8 d in milk) and 14 were late-lactation cows (LL; 269 ± 30 d in milk). Cows were fed once daily, and DMI was determined for the first 4 h after feeding. Liver and blood samples were collected before feeding and 4 h after feeding. Feed intake over the 4-h period ranged from 3.7 to 9.6 kg of dry matter and was similar for the 2 stages of lactation. Before feeding, hepatic AcCoA content was greater for PP compared with LL cows (34.4 vs. 12.5 nmol/g), and decreased over the 4 h after feeding for PP only (28.7 vs. 34.4 nmol/g). The range for change in AcCoA over the 4-h period was wide for both PP (−24.3 to 10.4 nmol/g) and LL (−5.7 to 16.1 nmol/g), and was related negatively to DMI at 4 h for both PP (R² = 0.55) and LL (R² = 0.31). The reduction in plasma NEFA concentration over the 4-h period was greater for PP than LL cows (−681 vs. −47 µEq/L), and was related to DMI at 4 h for both PP and LL (both R² = 0.38). Greater DMI among cows over the first 4 h after feeding might have been from a sharper reduction in supply of AcCoA in the liver for oxidation during meals because of the reduction in plasma NEFA concentration. Consistent with this is that the change in AcCoA was positively related to the reduction in plasma NEFA concentration for PP cows (R² = 0.31). However, change in plasma NEFA concentration was not related to change in hepatic AcCoA in LL cows, indicating that the pool of AcCoA in LL cows is not as dependent on NEFA flux to the liver as that of PP cows. Further research is required to determine production and fate of AcCoA within the timeframe of meals and the effects of feeding on energy charge in hepatic tissue.
When do we eat? Ingestive behavior, survival, and reproductive success
2013, Hormones and Behavior
The neuroendocrinology of ingestive behavior is a topic central to human health, particularly in light of the prevalence of obesity, eating disorders, and diabetes. The study of food intake in laboratory rats and mice has yielded some useful hypotheses, but there are still many gaps in our knowledge. Ingestive behavior is more complex than the consummatory act of eating, and decisions about when and how much to eat usually take place in the context of potential mating partners, competitors, predators, and environmental fluctuations that are not present in the laboratory. We emphasize appetitive behaviors, actions that bring animals in contact with a goal object, precede consummatory behaviors, and provide a window into motivation. Appetitive ingestive behaviors are under the control of neural circuits and neuropeptide systems that control appetitive sex behaviors and differ from those that control consummatory ingestive behaviors. Decreases in the availability of oxidizable metabolic fuels enhance the stimulatory effects of peripheral hormones on appetitive ingestive behavior and the inhibitory effects on appetitive sex behavior, putting a new twist on the notion of leptin, insulin, and ghrelin “resistance.” The ratio of hormone concentrations to the availability of oxidizable metabolic fuels may generate a critical signal that schedules conflicting behaviors, e.g., mate searching vs. foraging, food hoarding vs. courtship, and fat accumulation vs. parental care. In species representing every vertebrate taxa and even in some invertebrates, many putative “satiety” or “hunger” hormones function to schedule ingestive behavior in order to optimize reproductive success in environments where energy availability fluctuates.
Hypophagic effects of propionate increase with elevated hepatic acetyl coenzyme A concentration for cows in the early postpartum period
2012, Journal of Dairy Science
Citation Excerpt :
Although propionate might also decrease transport of LCFA into the mitochondria, inhibiting β-oxidation, this is inconsistent with effects of inhibiting or enhancing β-oxidation on feed intake as reviewed by Allen et al. (2009). Inhibiting transport of LCFA into the mitochondria by blocking CPT1 with methyl palmoxirate (Friedman et al., 1986) stimulated eating in rats, whereas stimulating transport of LCFA into the mitochondria by supplementation of carnitine to transition dairy cows decreased feed intake during the first 2 wk of lactation (Carlson et al., 2007). The hypophagic effects of propionate, but not acetate, were increasingly pronounced at elevated concentrations of hepatic acetyl CoA (Figure 2).
Thirty multiparous lactating dairy cows were used in a randomized block design experiment to evaluate factors related to the degree of hypophagia from intraruminal infusion of propionate. Cows between 3 and 40 d postpartum at the start of the experiment were blocked by calving date and randomly assigned to treatment. Treatments were 1.0 mol/L propionic acid or 1.0 mol/L acetic acid adjusted to pH 6 with sodium hydroxide and infused at 0.5 mol of volatile fatty acid/h from 6 h before feeding until 12 h after feeding. Propionate infusion decreased dry matter intake by 20.0%, total metabolizable energy intake by 22.5%, and plasma β-hydroxybutyrate concentration by 54.3% compared with acetate infusion. Effects of treatment on dry matter intake were related to concentration of acetyl coenzyme A (CoA) in the liver; hypophagic effects of propionate compared with acetate increased as liver acetyl CoA concentration increased. Hypophagic effects of propionate are greater for cows with elevated concentrations of acetyl CoA in the liver.
Energy partitioning, ingestive behavior, and reproductive success
2009, Hormones, Brain and Behavior Online
Gonadal hormones have profound effects on energy metabolism. Energy metabolism, in turn, controls the synthesis and secretion of the sex hormones. In addition to having reversible effects on energy metabolism in adults, sex hormones in utero set developmental events in motion that determine sexually dimorphic, lifelong patterns of body fat distribution. These patterns of body fat distribution are strongly associated with the prevalence of disease and mortality. To understand obesity-associated disease we must understand the link to reproduction. This chapter describes this link in terms of three levels of organization: (1) primary metabolic sensory signals generated by the oxidation of metabolic fuels, (2) hormones that act as mediators between the metabolic stimulus and the central effectors, (3) hormones that modulate the metabolic stimulus, and (4) the central effectors for ingestive behavior and reproduction. Hormones, including the so-called sex hormones, modulate reproduction and ingestive behavior by changing the disposition of metabolic fuels. Hormones such as insulin, glucagon, leptin, ghrelin, and the gonadal hormones determine energy partitioning, that is, they direct metabolic fuels into or out of storage. Mechanisms that control ingestive and sex behavior are sensitive to the availability of oxidizable fuels, and when hormone levels promote the uptake and storage of those fuels, the deficit in oxidizable fuels stimulates hunger and inhibits reproduction. Progress in understanding energy balance, appetite, and obesity will be facilitated by understanding the relationship to reproductive success.

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Meeting reportIntegrated metabolic control of food intake

Abstract

Physiol Behav

Physiol Behav

Am J Clin Nutr

J Biol Chem

Physiol Behav

J Biol Chem

Effects of 2-deoxyglucose on carbohydrate metabolism: Review of the literature and studies in rats

Physiol Behav

Hyperphagia in rats with experimental diabetes mellitus: A response to a decreased supply of utilizable fuels

J Comp Physiol Psychol

Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding

Am J Physiol

The physiological psychology of hunger: a physiological perspective

Psychol Rev

Meeting report
Integrated metabolic control of food intake