Substrate cycling between triglyceride and fatty acid in human adipocytes

Hammond, Vanessa A.; Johnston, Desmond G.

doi:10.1016/0026-0495(87)90199-5

Cited by 58 publications

(44 citation statements)

References 20 publications

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“…It is notable that the estimated total body fat cell thermogenesis, as calculated from cellular heat production and known values for total body fat cell number, 15 does not exceed 5% of the resting metabolic rate under basal and 7% under stimulated conditions. Indeed, these calculated values are in good agreement with data derived from in vivo studies.…”

Section: Implications For the Whole Bodymentioning

confidence: 90%

“…19,23 Re-esteri®cation rate of FFA (R RE ) was calculated from the lipolytic rate (R GLL ) and the rate of FFA release (R FFA ) according to the formula R RE 3 6 R GLL 7 R FFA . 15 …”

Section: Biochemcial Analysesmentioning

confidence: 99%

“…Yet, the relationship between fat cell and total body thermogenesis is made complex by the fact that massive obesity is accompanied by an increased fat cell number. 15,44 According to a computer generated numerical simulation, 45 an about 20% reduction of the resting metabolic rate would be necessary to make a lean person obese, provided that energy intake remains unchanged. This could be the case if the energy expenditure of all body cells would be uniformly reduced by the same extent as in the fat cells examined in the present study.…”

Section: Implications For the Whole Bodymentioning

confidence: 99%

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Decreased white fat cell thermogenesis in obese individuals

Böttcher

Fürst

1997

Int J Obes

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OBJECTIVE: To investigate whether white adipocyte thermogenesis and energy metabolism are reduced in obese individuals. SUBJECTS: Eight lean and 15 obese men and women; BMI 19±41. DESIGN: Isolated subcutaneous adipocytes were maintained in agarose gel for 20 h under basal conditions and subsequently for 10 h after stimulation with 1 mM isoprenaline. Direct microcalorimetry was performed continuously over 30 h while biochemical measures were obtained after 0, 20, 25 and 30 h. MEASUREMENTS: Total cellular thermogenesis, oxygen consumption, glycolysis, lipolysis, triglyceride/FFA substrate cycle, adenine nucleotides, DNA content as basis of reference. RESULTS: Under basal and stimulated conditions, thermogenesis (5.6 and 8.6 mW/mgDNA, respectively; P < 0.0001) correlated negatively (P < 0.01 and P < 0.05, respectively) with the BMI and positively with O 2 and glucose consumption, lactate, glycerol, FFA release and FFA re-esteri®cation. Reduced basal lactate production with increased BMI (P < 0.05) indicates a more aerobic adipocyte metabolism in obese individuals. Negative correlation between BMI and stimulated triglyceride/FFA substrate cycle activity (P < 0.01) explains the decreased hormone induced adipocyte heat production in the obese. CONCLUSIONS: The results suggest that a reduction of total body energy expenditure, which is discussed to cause obesity, can be associated with distinct metabolic alterations at a cellular level. However, since the estimated total body fat cell thermogenesis does not exceed 7% of the resting metabolic rate, the observed decrease of adipocyte heat production in the face of augmented BMI can only in part be responsible for the development of obesity.

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Section: Implications For the Whole Bodymentioning

confidence: 90%

“…19,23 Re-esteri®cation rate of FFA (R RE ) was calculated from the lipolytic rate (R GLL ) and the rate of FFA release (R FFA ) according to the formula R RE 3 6 R GLL 7 R FFA . 15 …”

Section: Biochemcial Analysesmentioning

confidence: 99%

Section: Implications For the Whole Bodymentioning

confidence: 99%

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Decreased white fat cell thermogenesis in obese individuals

Böttcher

Fürst

1997

Int J Obes

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“…In humans the activity of this cycle ranges enormously from 0 to 100% re-esterification of released fatty acids (54) and is regulated through environmental (diet, exercise) (55), anatomic (gender and adipose tissue site) (56), and hormonal influences (57). A number of hormones, such as norepinephrine and insulin have been shown to modulate the triglyceride/fatty acid cycle in adipose tissue, as well as other substrate cycles in additional tissues (56,57).…”

Section: Discussionmentioning

confidence: 99%

Acylation-stimulating Protein (ASP) Deficiency Induces Obesity Resistance and Increased Energy Expenditure in ob/obMice

Xia

Sniderman

Cianflone

2002

Journal of Biological Chemistry

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Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. In mice, C3 (the precursor to ASP) knockout results in ASP deficiency and leads to reduced body fat and leptin levels. The protective potential of ASP deficiency against obesity and involvement of the leptin pathway were examined in ob/ob C3(؊/؊) double knockout mice (2KO). Compared with agematched ob/ob mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance; associated with decreased body weight (4 -17 weeks age: male: ؊13.7%, female: ؊20.6%, p < 0.0001) and HOMA (homeostasis model assessment) index (؊37.7%), suggesting increased insulin sensitivity. By contrast, food intake in 2KO mice was ؉9.1% higher over ob/ob mice (p < 0.001, 2KO 5.1 ؎ 0.2 g/day, ob/ob 4.5 ؎ 0.2 g/day, wild type 2.6 ؎ 0.1 g/day). The hyperphagia/leanness was balanced by a 28.5% increase in energy expenditure (oxygen consumption: 2KO, 131 ؎ 8.9 ml/h; ob/ob, 102 ؎ 4.5 ml/h; p < 0.01; wild type, 144 ؎ 8.9 ml/h). These results suggest that the ASP regulation of energy storage may influence energy expenditure and dynamic metabolic balance.Acylation-stimulating protein (ASP) 1 is an adipocyte-derived protein that has potent anabolic effects on human adipose tissue for both glucose uptake and non-esterified fatty acid (NEFA) storage (1, 2). This occurs via translocation of glucose transporters (GLUT1, GLUT3, and GLUT4) from intracellular sites to the cell surface (3, 4) and an increase in diacylglycerol acyltransferase (DGAT) activity (2). These effects appear to be mediated through specific cell surface binding (6, 7), resulting in activation of a signaling pathway that includes protein kinase C (8). In addition, ASP has been shown to inhibit hormone-sensitive lipase in adipocytes, independently and additively to insulin (9). There is a differentiation-dependent increase in ASP binding and ASP response in adipocytes (1). The major site of action of ASP is adipocytes, as determined by competitive binding, stimulation of triglyceride synthesis, enhanced glucose transport, and transporter translocation (6).ASP is identical to C3adesArg, a cleavage product of complement C3. Cleavage of complement C3 is mediated through the alternate complement pathway via the interaction of C3, factor B, and adipsin that generates C3a. Rapid cleavage of the Cterminal arginine of C3a by carboxypeptidase N generates ASP (10). Adipocytes are one of the few cells capable of producing all three factors (factor B, adipsin, and C3) that are required for the production of ASP (11). ASP production increases consequent to adipocyte differentiation (13), and plasma ASP levels are elevated in obesity (14, 15). Chylomicrons in vitro stimulate ASP production by adipocytes (16,17). In vivo arterial-venous gradients across a subcutaneous adipose tissue bed in humans demonstrate direct postprandial production of ASP (18). The postprandial increase in ASP is adipose tissue specifi...

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“…However, even in the fasted state, up to 65% of the generated FFA is re-esterified back into TG . A substantial part of the re-esterification occurs already within the adipocytes (Hammond & Johnston 1987), and in contrast to the fed state, G3P is not derived from glucose, which is saved for metabolism by other tissues. Instead, the G3P used for re-synthesis of TG is primarily derived from glyceroneogenesis, which is a truncated form of gluconeogenesis that uses lactate, pyruvate, and alanine to generate G3P (reviewed in and Reshef et al (2003); Fig.…”

Section: Glycerol Metabolismmentioning

confidence: 99%

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

Lebeck

2014

Journal of Molecular Endocrinology

106

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Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver. Glycerol metabolismThe metabolic switching between feeding and fasting is central to everyday life and involves tight hormonal control with effects on muscle, adipose tissue, and liver that maintains an adequate handling of metabolic precursors to support energy demands. One of the molecules affected by metabolic switching is glycerol, which is a small 3-carbon alcohol that in the fed state is stored as the backbone of triglyceride (TG) mainly in adipose tissue.In the fed state, after ingestion of dietary fats (w90% TG), !30% of TG is fully hydrolyzed into free fatty acids (FFA) and glycerol. Glycerol rapidly enters the enterocytes of the small intestine and thereafter the circulation through the portal vein and is primarily metabolized by the liver (Lin 1977). In adipose tissue, the activity of glycerol kinase (GlyK), that catalyzes the initial phosphorylation of glycerol into glycerol-3-phosphate (G3P), is negligible and therefore glycerol is not normally utilized in adipose tissue. Instead G3P used for the synthesis of TG in the fed state is derived from glycolysis.During states of increased energy demand, such as fasting and exercise, adipocyte lipolysis is increased by activation of adipose TG lipase and hormone-sensitive

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Substrate cycling between triglyceride and fatty acid in human adipocytes

Cited by 58 publications

References 20 publications

Decreased white fat cell thermogenesis in obese individuals

Decreased white fat cell thermogenesis in obese individuals

Acylation-stimulating Protein (ASP) Deficiency Induces Obesity Resistance and Increased Energy Expenditure in ob/obMice

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

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