Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.

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Obesity alters gut microbial ecology

Essential fatty acids in health and chronic disease

Thermogenic mechanisms in brown fat.

Obesity results when energy intake exceeds energy expenditure Naturally occurring genetic mutations, as well as ablative lesions, have shown that the brain regulates both aspects of energy balance and that abnormalities in energy expenditure contribute to the development of obesity Energy can be expended by performing work or producing heat (thermogenesis) Adaptive thermogenesis, or the regulated production of heat, is influenced by environmental temperature and diet Mitochondria, the organelles that convert food to carbon dioxide, water and ATP, are fundamental in mediating effects on energy dissipation Recently, there have been significant advances in understanding the molecular regulation of energy expenditure in mitochondria and the mechanisms of transcriptional control of mitochondrial genes Here we explore these developments in relation to classical physiological views of adaptive thermogenesis

Towards a molecular understanding of adaptive thermogenesis.

Lipid Biosynthesis in the Chick. A Consideration of Site of Synthesis, Influence of Diet and Possible Regulatory Mechanisms

Leptin, the ob gene product, is released from adipose tissue and likely acts in the central nervous system, particularly within the hypothalamus, to exert many of its effects. Obesity in C57BL/6J ob/ob mice is caused by a mutation in the ob gene resulting in a lack of functional leptin. In this study, we first compared effects of a single intracerebroventricular (ICV) injection of 3 pmol (50 ng) or 60 pmol (1 microg) leptin on food intake and oxygen consumption of lean and ob/ob mice deprived of food for 4 h during the 48-h period postinjection. Injection of 3 pmol leptin minimally lowered food intake in these mice without influencing oxygen consumption. Injection of 60 pmol of leptin rapidly lowered food intake within 30 min in both lean and ob/ob mice, with effects persisting for 24 h. Lean and ob/ob mice treated with leptin consumed 40 and 60% less food, respectively, in 24 h than vehicle-treated controls. Injection of leptin (60 pmol ICV) suppressed food intake of adrenalectomized mice as well (by 25 and 40% in lean mice and by 20 and 68% in ob/ob mice at 3 and 24 h, respectively), indicating that glucocorticoids are not essential for leptin to suppress food intake. Leptin increased oxygen consumption in conditions in which diet-induced thermogenesis was low, i.e., in fed ob/ob mice and in food-deprived lean mice, but not in fed adrenalectomized ob/ob mice or in fed lean mice. ICV injection of 60 pmol leptin along with 230 pmol (2 microg) of neuropeptide Y (NPY) attenuated NPY-induced feeding in ob/ob, but not in lean mice, suggesting an enhanced potential for crosstalk between the leptin and NPY signaling systems in ob/ob mice lacking endogenous leptin. Leptin exerts rapid-onset actions within the central nervous system to coordinate control of food intake and metabolic rate.

Leptin Rapidly Lowers Food Intake and Elevates Metabolic Rates in Lean and ob/ob Mice

Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to maximize food intake and also maintain high thermoregulatory metabolic rates to optimize survival, sug...

https://www.physiology.org/doi/pdf/10.1152/ajpregu.1999.277.3.R742

Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice.

Reduced sympathetic nervous system activity in rats with ventromedial hypothalamic lesions.

The effect of fasting on blood metabolites and glucose metabolism in the chicken was studied. Parameters of glucose metabolism were estimated in vivo using a single injection of [2-3H]-glucose or [6-3H]-glucose in combination with [U-14C]-glucose. Plasma glucose, blood lactate and blood acetoacetate levels were not significantly changed in chickens fasted for 72 hours. Pyruvate levels in chickens fasted for 24 hours were higher than those observed in blood from birds fasted 0 to 72 hours. Further, the lactate to pyruvate ratio was lower in chickens fasted for 24 to 72 hours than in fed chickens. Fasting chickens for 24 or 72 hours resulted in three- to fivefold increase in blood beta-hydroxybutyrate levels and a significant increase in beta-hydroxybutyrate to acetoacetate ratio. Plasma levels of alanine and serine were increased after a 24 hour fast but were not further changed when fasting was extended to 72 hours. Plasma aspartate and glutamate levels were not significantly changed in chickens fasted for 24 hours but were markedly decreased in chickens fasted for 72 hours. Plasma levels of glycine were significantly lower in chickens fasted 24 or 72 hours than in fed birds. Glucose replacement rates estimated with [2-3H]-glucose in chickens fasted 0,24 and 72 hours were 14.3, 9.1 and 9.4 mg glucose/minute/kg body weight, respectively. Fasting up to 72 hours did not influence the total body glucose mass in the chickens. The degree of glucose-carbon recycling in 24-hour fasted chickens estimated by using [2-3H]- and [U-14C]-glucose or [6-3H]- and [U-14C]-glucose averaged 42% to 52% and 27% to 30%, respectively. These observations indicate that rate of glucose utilization in the chicken is rapid and that substantial recycling of glucose carbon occurs in fasted chickens.

Dale R. Romsos

Papers

Lipid Biosynthesis in the Chick. A Consideration of Site of Synthesis, Influence of Diet and Possible Regulatory Mechanisms

Leptin Rapidly Lowers Food Intake and Elevates Metabolic Rates in Lean and ob/ob Mice

Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice.

Reduced sympathetic nervous system activity in rats with ventromedial hypothalamic lesions.

Blood Metabolites and Glucose Metabolism in the Fed and Fasted Chicken