Do fat babies stay fat?

A total of 203 children included in a study of feeding practices and weight in infancy were reviewed four to five years later. Although in infancy 28 (14%) of the children were obese and a further 52 (26%) overweight, in childhood most were of normal weight and fatness, with only 5 (2-5%) obese and 22 (11%) overweight, Three of the five obese children were also obese as infants, but only one in nine obese infants was obese at 5 years. Weight in infancy does not necessarily indicate later body size. Tall stature of the children was probably related to their socioeconomic environment.     

Electrical coupling between fat cells in newt fat body and mouse brown fat

White fat from the newt, Triturus pyrrhogaster, fat body, and brown fat from the interscapular fat pad of newborn mice have been tested for the presence of low-resistance intercellular junctions. 42 pairs of amphibian fat cells and 15 pairs of mammalian brown fat cells were found to be "electrically coupled." In most of these cases intracellular deposition of a dye, Niagara Sky Blue: 6B, was used to supplement and confirm direct observations of impalements. Coupling was often difficult to find in both preparations, but the mechanical disturbance of the tissue during the preparative procedures may have uncoupled many cells. The fact that, in both types of fat, coupling was observed between cells separated by one or more other cells suggests that coupling may be more widespread in vivo. Electron microscopy (provided by Dr. J. -P. Revel and Mrs. K. Wolken) of the brown fat revealed frequent intercellular junctions resembling "gap junctions" but possibly lacking the substructure usually visible with colloidal lanthanum infiltration. The results are discussed in relation to current ideas about the exchange of regulatory molecules via low-resistance junctions and about the control of brown fat by hormones and nerves.     

Hyperleptinemia depletes fat from denervated fat tissue.

Adenovirus-mediated transfer of the leptin gene causes severe hyperleptinemia with rapid disappearance of visible body fat. To determine if this dramatic lipopenic action is mediated by neurotransmitted signals from the central nervous system, we transplanted the right epididymal fat pad of normal rats to the anterior abdominal wall. Four weeks later, rats were infused with either adenovirus-leptin cDNA (AdCMV-leptin) or adenovirus-beta-galactosidase (AdCMV-beta-gal). Eight days later, plasma leptin averaged 23 +/- 12 ng/ml in the former and 1.2 +/- 0.4 ng/ml in the latter. The fat transplant was intact in all 4 AdCMV-beta-gal-infused rats but had disappeared in all 4 hyperleptinemic rats. Tyrosine hydroxylase staining of the fat pad remnant was negative, excluding regrowth of sympathetic nerves. Thus, the lipopenic action of severe hyperleptinemia on adipocytes is not mediated by neurotransmitters, but must have resulted either from direct action of leptin and/or from leptin-mediated neurohormones.     

Intestinal absorption of fat

Summary It is generally accepted that between 50 and 70% of the fatty acids of ingested triglycerides are hydrolyzed prior to absorption and yet migration between the 2 and 1,3 positions is minimal. The occurrance of the monoglyceride pathway for triglyceride biosynthesis provides a logical explanation for these findings. In addition, this sequence provides a logical explanation of the particulate and lipolytic theories. Triglycerides are hydrolyzed at the 1 and 3 positions giving rise to fatty acids and 2-monoglycerides, which in combination with bile salts form micelles and penetrate the intestinal membrane. The fatty acids are activated to the respective CoA derivatives and acylate the 2-monoglyceride forming triglycerides. The triglyceride thus synthesized, has a similar chemical structure with regard to the 1,3 and 2 position as the original triglyceride. The triglyceride is coated with a-lipoprotein and is transformed into chylomicrons which enter the thoracic duct lymph.It is suggested that this mechanism be referred to as the PARLIP sequence since, particles in the form of micelles are involved in the absorption, and in addition a considerable amount of lipolysis occurs. This terminology would represent a scientific merger of the particulate and the lipolytic theories into a common sequence, while maintaining some identity in recognition of the numerous investigations that have occurred in the past 100 years to support these two basic postulates.     

Genome-wide association of pericardial fat identifies a unique locus for ectopic fat

Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.     

A simple culture method of fat cells from mature fat tissue fragments

To obtain immature fat cells in vitro, we used a primary culture of undigested mature fat tissue fragments. The immature fat cells, i.e., fibroblast-like fat cells, proliferated extensively from the fat tissue and differentiated after reaching confluence. The process of differentiation was assumed by the development of intracytoplasmic lipid droplets and by the triglyceride content in the cells. Cellular differentiation was induced in high percentages (over 70-80%) of the cells in the medium containing high glucose concentrations (200 mg/dl) supplemented with 10-20% newborn calf serum. The intracellular accumulation of triglyceride was also enhanced by insulin administration. In these cells, a reciprocal relationship was observed between proliferation and differentiation. Fibroblast-like fat cells derived from mature fat tissue in this simple culture system are suitable for the study of the proliferation and differentiation of immature fat cells.     

Making fat work

The burgeoning obesity and metabolic disease epidemics in the developed world are exerting a terrible toll on society, yet the precise mechanisms responsible for the emergence of these dramatic trends over a relatively short period of time remain poorly understood. Philip A.Wood's book How Fat Works provides important insights into cellular lipid metabolism, as well as discussing some of the important external contributors to the development of human obesity. The foundation provided by this book allows for the exploration of how body fat has gone from hero during the millennia when starvation was the paramount nutritional risk to its current role as villain in our period of caloric excess. With the incredible personal and societal costs brought about by excess body weight, a comprehensive understanding of the mechanisms responsible for obesity is fundamentally necessary if we are to reverse these dire trends. Here, we delve deeper into some of the forces contributing to the obesity epidemic and discuss some individual measures as well as public policy decisions that may help reverse weight trends, while specifically focusing on the growing problem of pediatric obesity.